Category Archives: Cell Medicine

GAITHERSBURG, Md., Sept. 1, 2020 /PRNewswire/ --Cartesian Therapeutics, a fully integrated, clinical-stage biopharmaceutical company developing cell and gene therapies for cancer, autoimmune diseases and respiratory diseases, today announced that it has initiated a Phase 1/2 clinical trial of its lead RNA-engineered mesenchymal stem cell (MSC) therapy, Descartes-30, in patients with moderate-to-severe acute respiratory distress syndrome (ARDS), including that caused by COVID-19. Based upon the company's research and analysis, this program is understood to be the first RNA-engineered cell therapy to enter clinical development for ARDS and COVID-19. It is also the first cell therapy to specifically degrade NETs, webs of extracellular DNA and histones that entrap inflammatory cells, block alveoli and vessels, and drive the pathogenesis of ARDS and COVID-19.

"Patients with ARDS, especially those with COVID-19 ARDS, generate copious amounts of NETs that physically obstruct alveoli and vessels, which leads to respiratory distress, immune-mediated thrombosis and a vicious cycle of inflammation," said Bruce Levy, MD, Chief of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital and Parker B. Francis Professor at Harvard Medical School, and a clinical investigator in the Descartes-30 trial. "We would therefore expect that degrading NETs would improve oxygenation as well as resolve thrombi and quell inflammation in these patients. If successful, Descartes-30 would be a highly differentiated game-changer within our limited toolkit in managing this exceedingly difficult condition."

Descartes-30 is an off-the-shelf (allogeneic) MSC product engineered with Cartesian's RNA ArmorySM cell therapy platform. By expressing a unique combination of DNases that work synergistically, Descartes-30 can eliminate large, macroscopic amounts of NETs within minutes. MSCs are inherently immunomodulatory and naturally travel to the lungs, where they are expected to provide continuous, local delivery of DNases to NET-laden lung tissue.

"We engineered Descartes-30 without genomic modification, and therefore the production of DNases is expected to be time-limited to match the acute nature of ARDS," said Metin Kurtoglu, MD, PhD, Chief Medical Officer at Cartesian. "Given thatDescartes-30will produce DNases locally and transiently, we anticipate that it will have a favorable benefit-to-risk profile. We also anticipate that these properties will enable Descartes-30 to treat a wide array of NET-related autoimmune and cardiovascular diseases."

About the Phase 1/2a Clinical Trial

The "Phase 1/2a Study of Descartes-30 in Acute Respiratory Distress Syndrome" (NCT04524962) is enrolling patients with ARDS at multiple critical care units in the United States. Patients with ARDS due to COVID-19 are given enrollment priority. This first-in-human study aims to determine the safety and preliminary efficacy of Descartes-30 in patients with moderate to severe ARDS. The study, which is estimated to begin treatment in September, aims to enroll approximately 20 patients prior to initiation of a larger study. For more information visit http://www.cartesiantherapeutics.com/Descartes-30-ARDS.

About ARDS and NETs

ARDS is a severe inflammatory lung disease with a mortality of over 40%. Inflammation leads to injury of lung tissue and leakage of blood and plasma into air spaces, resulting in low oxygen levels and often requiring mechanical ventilation. Inflammation in the lung may lead to inflammation elsewhere, causing shock and injury or dysfunction in the kidneys, heart, and muscles. Some causes of ARDS include COVID-19, severe pneumonia (including influenza), sepsis, trauma, and smoke inhalation.

NETs are inflammatory webs of DNA and proteins produced by neutrophils. NETs are commonly found in ARDS and are thought to exacerbate the disease by physically occluding air spaces and vessels, leading to reduced oxygenation and increased risk of immune thrombi. NETs are implicated in a variety of conditions beyond ARDS, including autoimmune and cardiovascular diseases.

About the RNA ArmorySM

The RNA ArmorySM is Cartesian's proprietary RNA-based cell engineering platform that activates and arms cells with carefully selected, mRNA-based therapeutics. Unmodified donor cells enter the RNA ArmorySMin the millions; a battle-ready cell army leaves the RNA ArmorySMin the tens of billions. Each cell is equipped with a combination of therapeutics rationally chosen to have a synergistic effect on the disease. In the body, the cells deliver a precision-targeted treatment regimen directly to the site of disease. The cells express therapeutics with a defined half-life, enhancing their safety profile and making repeat dosing and outpatient administration possible. The platform is agnostic to cell type: we choose the best cell for the job, whether autologous or off-the shelf. For more information visithttps://www.cartesiantherapeutics.com/rna-armory/.

About Cartesian Therapeutics

Founded in 2016,Cartesianis a fully integrated, clinical-stage biopharmaceutical company developing potent yet safer cell and gene therapies designed to benefit the broadest range of patients with cancer, autoimmune and respiratory diseases. Cartesianhas three products in clinical development under four open investigational new drug application (INDs) with the U.S. Food & Drug Administration (FDA). All investigational therapies are manufactured at Cartesian's wholly owned, state-of-the-art cGMP manufacturing facility in Gaithersburg, MD.Cartesian's commanding IP position benefits in part from a broad, exclusive patent license from the National Cancer Institute. For more information visithttps://www.cartesiantherapeutics.com/clinical-trials/.

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SOURCE Cartesian Therapeutics

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Cartesian Therapeutics Initiates Clinical Trial of First RNA-Engineered Cell Therapy for Acute Respi - PharmiWeb.com

PLYMOUTH MEETING, Pa., Sept. 1, 2020 /PRNewswire/ --INOVIO (NASDAQ:INO), a biotechnology company focused on bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases and cancer, today announced that Dr. J. Joseph Kim, President and CEO, along with other members of INOVIO management, will present at the following investor conferences in September:

H.C. Wainwright 22nd Annual Global Investment Conference Date: Monday, September 14, 2020Time: 9:30 a.m. ETPresentation Format: Corporate Presentation

Cantor Global Healthcare ConferenceDate: Thursday, September 17, 2020Time: 10:40 a.m. ETPresentation Format: Fireside Chat

Oppenheimer Fall Healthcare Life Sciences & MedTech SummitDate: Wednesday, September 23, 2020Time: 10:50 a.m. ETPresentation Format: Fireside Chat

Live and archived versions of the virtual presentations will be available through the INOVIO Investor Relations Events page and may be accessed by visiting INOVIO's website at http://ir.inovio.com/investors/events/default.aspx. All presentation times are subject to change.

About INOVIO's DNA Medicines Platform

INOVIO has 15 DNA medicine clinical programs currently in development focused on HPV-associated diseases, cancer, and infectious diseases, including coronaviruses associated with MERS and COVID-19 diseases being developed under grants from the Coalition for Epidemic Preparedness Innovations (CEPI) and the U.S. Department of Defense. DNA medicines are composed of optimized DNA plasmids, which are small circles of double-stranded DNA that are synthesized or reorganized by a computer sequencing technology and designed to produce a specific immune response in the body.

INOVIO's DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using INOVIO's proprietary hand-held smart device called CELLECTRA. The simple-to-use CELLECTRA device provides a brief electrical pulse to reversibly open small pores in the local skin area cells resulting in more than a hundred-fold increase in product delivery providing dose sparing and consistency. Once inside the cell, the DNA plasmids instruct the cell to produce the targeted antigen. The antigen is processed naturally in the cell and triggers a specific T cell and antibody-mediated immune responses. Administration with the CELLECTRA device, which takes only a few seconds,is designed to ensure that the DNA medicine is efficiently delivered directly into the body's cells, where it can go to work to drive an immune response. INOVIO's DNA medicines are transient, and do not interfere with or change in any way an individual's own DNA. The advantages of INOVIO's DNA medicine platform are how fast DNA medicines can be designed and manufactured; the stability of the products, which do not require freezing in storage and transport; and the consistent immune response, safety profile, and tolerability that have been observed in clinical trials with multiple products.

With more than 2,000 patients receiving INOVIO investigational DNA medicines in more than 7,000 applications across a range of clinical trials, INOVIO has a strong track record of rapidly generating DNA medicine candidates with potential to meet urgent global health needs.

About INOVIO

INOVIO is a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases, cancer, and diseases associated with HPV. INOVIO is the first and only company to have clinically demonstrated that a DNA medicine can be delivered directly into cells in the body via a proprietary smart device to produce an efficacious, robust and tolerable immune response. Specifically, INOVIO's lead candidate VGX-3100, currently in Phase 3 trials for precancerous cervical dysplasia, destroyed and cleared high-risk HPV 16 and 18 in a Phase 2b clinical trial. High-risk HPV is responsible for 70% of cervical cancer, 91% of anal cancer, and 69% of vulvar cancer. Also in development are programs targeting HPV-related cancers and a rare HPV-related disease, recurrent respiratory papillomatosis (RRP); non-HPV-related cancers glioblastoma multiforme (GBM) and prostate cancer; as well as externally funded infectious disease DNA vaccine development programs in Zika, Lassa fever, Ebola, HIV, and coronaviruses associated with MERS and COVID-19 diseases. Partners and collaborators include Advaccine, ApolloBio Corporation, AstraZeneca, The Bill & Melinda Gates Foundation, Coalition for Epidemic Preparedness Innovations (CEPI), Defense Advanced Research Projects Agency (DARPA)/Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND)/Department of Defense (DOD), GeneOne Life Science/VGXI, HIV Vaccines Trial Network, International Vaccine Institute (IVI), Medical CBRN Defense Consortium (MCDC), National Cancer Institute, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Ology Bioservices, the Parker Institute for Cancer Immunotherapy, Plumbline Life Sciences, Regeneron, Richter-Helm BioLogics, Roche/Genentech, University of Pennsylvania, Walter Reed Army Institute of Research, and The Wistar Institute. INOVIO also is a proud recipient of 2020 Women on Boards "W" designation recognizing companies with more than 20% women on their board of directors. For more information, visit http://www.inovio.com.

CONTACTS:

Media: Jeff Richardson, 267-440-4211, jrichardson@inovio.comInvestors: Ben Matone, 484-362-0076, ben.matone@inovio.com

* * * *

This press release contains certain forward-looking statements relating to our business, including our plans to develop and manufacture DNA medicines, our expectations regarding our research and development programs, including the planned initiation and conduct of preclinical studies and clinical trials and the availability and timing of data from those studies and trials, and our ability to successfully manufacture and produce large quantities of our product candidates if they receive regulatory approval. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, our ability to secure sufficient manufacturing capacity to mass produce our product candidates, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or our collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2019, our Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured or commercialized, that final results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law.

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INOVIO to Present at Upcoming Investor Conferences in September - The Wellsboro Gazette

Efforts to use regenerative medicinewhich seeks to address ailments as diverse as birth defects, traumatic injury, aging, degenerative disease, and the disorganized growth of cancerwould be greatly aided by solving one fundamental puzzle: How do cellular collectives orchestrate the building of complex, three-dimensional structures?

While genomes predictably encode the proteins present in cells, a simple molecular parts list does not tell us enough about the anatomical layout or regenerative potential of the body that the cells will work to construct. Genomes are not a blueprint for anatomy, and genome editing is fundamentally limited by the fact that its very hard to infer which genes to tweak, and how, to achieve desired complex anatomical outcomes. Similarly, stem cells generate the building blocks of organs, but the ability to organize specific cell types into a working human hand or eye has been and will be beyond the grasp of direct manipulation for a very long time.

But researchers working in the fields of synthetic morphology and regenerative biophysics are beginning to understand the rules governing the plasticity of organ growth and repair. Rather than micromanaging tasks that are too complex to implement directly at the cellular or molecular level, what if we solved the mystery of how groups of cells cooperate to construct specific multicellular bodies during embryogenesis and regeneration? Perhaps then we could figure out how to motivate cell collectives to build whatever anatomical features we want.

New approaches now allow us to target the processes that implement anatomical decision-making without genetic engineering. In January, using such tools, crafted in my lab at Tufts Universitys Allen Discovery Center and by computer scientists in Josh Bongards lab at the University of Vermont, we were able to create novel living machines, artificial bodies with morphologies and behaviors completely different from the default anatomy of the frog species (Xenopus laevis) whose cells we used. These cells rebooted their multicellularity into a new form, without genomic changes. This represents an extremely exciting sandbox in which bioengineers can play, with the aim of decoding the logic of anatomical and behavioral control, as well as understanding the plasticity of cells and the relationship of genomes to anatomies.

Deciphering how an organism puts itself together is truly an interdisciplinary undertaking.

Deciphering how an organism puts itself together is truly an interdisciplinary undertaking. Resolving the whole picture will involve understanding not only the mechanisms by which cells operate, but also elucidating the computations that cells and groups of cells carry out to orchestrate tissue and organ construction on a whole-body scale. The next generation of advances in this area of research will emerge from the flow of ideas between computer scientists and biologists. Unlocking the full potential of regenerative medicine will require biology to take the journey computer science has already taken, from focusing on the hardwarethe proteins and biochemical pathways that carry out cellular operationsto the physiological software that enables networks of cells to acquire, store, and act on information about organ and indeed whole-body geometry.

In the computer world, this transition from rewiring hardware to reprogramming the information flow by changing the inputs gave rise to the information technology revolution. This shift of perspective could transform biology, allowing scientists to achieve the still-futuristic visions of regenerative medicine. An understanding of how independent, competent agents such as cells cooperate and compete toward robust outcomes, despite noise and changing environmental conditions, would also inform engineering. Swarm robotics, Internet of Things, and even the development of general artificial intelligence will all be enriched by the ability to read out and set the anatomical states toward which cell collectives build, because they share a fundamental underlying problem: how to control the emergent outcomes of systems composed of many interacting units or individuals.

Many types of embryos can regenerate entirely if cut in half, and some species are proficient regenerators as adults. Axolotls (Ambystoma mexicanum) regenerate their limbs, eyes, spinal cords, jaws, and portions of the brain throughout life. Planarian flatworms (class Turbellaria), meanwhile, can regrow absolutely any part of their body; when the animal is cut into pieces, each piece knows exactly whats missing and regenerates to be a perfect, tiny worm.

The remarkable thing is not simply that growth begins after wounding and that various cell types are generated, but that these bodies will grow and remodel until a correct anatomy is complete, and then they stop. How does the system identify the correct target morphology, orchestrate individual cell behaviors to get there, and determine when the job is done? How does it communicate this information to control underlying cell activities?

Several years ago, my lab found that Xenopus tadpoles with their facial organs experimentally mixed up into incorrect positions still have largely normal faces once theyve matured, as the organs move and remodel through unnatural paths. Last year, a colleague at Tufts came to a similar conclusion: the Xenopus genome does not encode a hardwired set of instructions for the movements of different organs during metamorphosis from tadpole to frog, but rather encodes molecular hardware that executes a kind of error minimization loop, comparing the current anatomy to the target frog morphology and working to progressively reduce the difference between them. Once a rough spatial specification of the layout is achieved, that triggers the cessation of further remodeling.

The deep puzzle of how competent agents such as cells work together to pursue goals such as building, remodeling, or repairing a complex organ to a predetermined spec is well illustrated by planaria. Despite having a mechanistic understanding of stem cell specification pathways and axial chemical gradients, scientists really dont know what determines the intricate shape and structure of the flatworms head. It is also unknown how planaria perfectly regenerate the same anatomy, even as their genomes have accrued mutations over eons of somatic inheritance. Because some species of planaria reproduce by fission and regeneration, any mutation that doesnt kill the neoblastthe adult stem cell that gives rise to cells that regenerate new tissueis propagated to the next generation. The worms incredibly messy genome shows evidence of this process, and cells in an individual planarian can have different numbers of chromosomes. Still, fragmented planaria regenerate their body shape with nearly 100 percent anatomical fidelity.

Permanent editingof the encoded target morphology without genomic editing reveals a new kind of epigenetics.

So how do cell groups encode the patterns they build, and how do they know to stop once a target anatomy is achieved? What would happen, for example, if neoblasts from a planarian species with a flat head were transplanted into a worm of a species with a round or triangular head that had the head amputated? Which shape would result from this heterogeneous mixture? To date, none of the high-resolution molecular genetic studies of planaria give any prediction for the results of this experiment, because so far they have all focused on the cellular hardware, not on the logic of the softwareimplemented by chemical, mechanical, and electrical signaling among cellsthat controls large-scale outcomes and enables remodeling to stop when a specific morphology has been achieved.

Understanding how cells and tissues make real-time anatomical decisions is central not only to achieving regenerative outcomes too complex for us to manage directly, but also to solving problems such as cancer. While the view of cancer as a genetic disorder still largely drives clinical approaches, recent literature supports a view of cancer as cells simply not being able to receive the physiological signals that maintain the normally tight controls of anatomical homeostasis. Cut off from these patterning cues, individual cells revert to their ancient unicellular lifestyle and treat the rest of the body as external environment, often to ruinous effect. If we understand the mechanisms that scale single-cell homeostatic setpoints into tissue- and organ-level anatomical goal states and the conditions under which the anatomical error reduction control loop breaks down, we may be able to provide stimuli to gain control of rogue cancer cells without either gene therapy or chemotherapy.

During morphogenesis, cells cooperate to reliably build anatomical structures. Many living systems remodel and regenerate tissues or organs despite considerable damagethat is, they progressively reduce deviations from specific target morphologies, and halt growth and remodeling when those morphologies are achieved. Evolution exploits three modalities to achieve such anatomical homeostasis: biochemical gradients, bioelectric circuits, and biophysical forces. These interact to enable the same large-scale form to arise despite significant perturbations.

N.R. FULLER, SAYO-ART, LLC

BIOCHEMICAL GRADIENTS

The best-known modality concerns diffusible intracellular and extracellular signaling molecules. Gene-regulatory circuits and gradients of biochemicals control cell proliferation, differentiation, and migration.

BIOELECTRIC CIRCUITS

The movement of ions across cell membranes, especially via voltage-gated ion channels and gap junctions, can establish bioelectric circuits that control large-scale resting potential patterns within and among groups of cells. These bioelectric patterns implement long-range coordination, feedback, and memory dynamics across cell fields. They underlie modular morphogenetic decision-making about organ shape and spatial layout by regulating the dynamic redistribution of morphogens and the expression of genes.

BIOMECHANICAL FORCES

Cytoskeletal, adhesion, and motor proteins inside and between cells generate physical forces that in turn control cell behavior. These forces result in large-scale strain fields, which enable cell sheets to move and deform as a coherent unit, and thus execute the folds and bends that shape complex organs.

The software of life, which exploits the laws of physics and computation, is enabled by chemical, mechanical, and electrical signaling across cellular networks. While the chemical and mechanical mechanisms of morphogenesis have long been appreciated by molecular and cell biologists, the role of electrical signaling has largely been overlooked. But the same reprogrammability of neural circuits in the brain that supports learning, memory, and behavioral plasticity applies to all cells, not just neurons. Indeed, bacterial colonies can communicate via ionic currents, with recent research revealing brain-like dynamics in which information is propagated across and stored in a kind of proto-body formed by bacterial biofilms. So it should really come as no surprise that bioelectric signaling is a highly tractable component of morphological outcomes in multicellular organisms.

A few years ago, we studied the electrical dynamics that normally set the size and borders of the nascent Xenopus brain, and built a computer model of this process to shed light on how a range of various brain defects arise from disruptions to this bioelectric signaling. Our model suggested that specific modifications with mRNA or small molecules could restore the endogenous bioelectric patterns back to their correct layout. By using our computational platform to select drugs to open existing ion channels in nascent neural tissue or even a remote body tissue, we were able to prevent and even reverse brain defects caused not only by chemical teratogenscompounds that disrupt embryonic developmentbut by mutations in key neurogenesis genes.

Similarly, we used optogenetics to stimulate electrical activity in various somatic cell types totrigger regeneration of an entire tadpole tailan appendage with spinal cord, muscle, and peripheral innervationand to normalize the behavior of cancer cells in tadpoles strongly expressing human oncogenes such as KRAS mutations. We used a similar approach to trigger posterior regions, such as the gut, to build an entire frog eye. In both the eye and tail cases, the information on how exactly to build these complex structures, and where all the cells should go, did not have to be specified by the experimenter; rather, they arose from the cells themselves. Such findings reveal how ion channel mutations result in numerous human developmental channelopathies, and provide a roadmap for how they may be treated by altering the bioelectric map that tells cells what to build.

We also recently found a striking example of such reprogrammable bioelectrical software in control of regeneration in planaria. In 2011, we discovered that an endogenous electric circuit establishes a pattern of depolarization and hyperpolarization in planarian fragments that regulate the orientation of the anterior-posterior axis to be rebuilt. Last year, we discovered that this circuit controls the gene expressionneeded to build a head or tail within six hours of amputation, and by using molecules that make cell membranes permeable to certain ions to depolarize or hyperpolarize cells, we induced fragments of such worms to give rise to a symmetrical two-headed form, despite their wildtype genomes. Even more shockingly, the worms continued to generate two-headed progeny in additional rounds of cutting with no further manipulation. In further experiments, we demonstrated that briefly reducing gap junction-mediated connectivity between adjacent cells in the bioelectric network that guides regeneration led worms to regenerate head and brain shapes appropriate to other worm species whose lineages split more than 100 million years ago.

My group has developed the use of voltage-sensitive dyes to visualize the bioelectric pattern memory that guides gene expression and cell behavior toward morphogenetic outcomes. Meanwhile, my Allen Center colleagues are using synthetic artificial electric tissues made of human cells and computer models of ion channel activity to understand how electrical dynamics across groups of non-neural cells can set up the voltage patterns that control downstream gene expression, distribution of morphogen molecules, and cell behaviors to orchestrate morphogenesis.

The emerging picture in this field is that anatomical software is highly modulara key property that computer scientists exploit as subroutines and that most likely contributes in large part to biological evolvability and evolutionary plasticity. A simple bioelectric state, whether produced endogenously during development or induced by an experimenter, triggers very complex redistributions of morphogens and gene expression cascades that are needed to build various anatomies. The information stored in the bodys bioelectric circuitscan be permanently rewritten once we understand the dynamics of the biophysical circuits that make the critical morphological decisions. This permanent editing of the encoded target morphology without genomic editing reveals a new kind of epigenetics, information that is stored in a medium other than DNA sequences and chromatin.

Recent work from our group and others has demonstrated that anatomical pattern memories can be rewritten by physiological stimuli and maintained indefinitely without genomic editing. For example, the bioelectric circuit that normally determines head number and location in regenerating planaria can be triggered by brief alterations of ion channel or gap junction activity to alter the animals body plan. Due to the circuits pattern memory, the animals remain in this altered state indefinitely without further stimulation, despite their wildtype genomes. In other words, the pattern to which the cells build after damage can be changed, leading to a target morphology distinct from the genetic default.

N.R. FULLER, SAYO-ART, LLC

First, we soaked a planarian in voltage-sensitive fluorescent dye to observe the bioelectrical pattern across the entire tissue. We then cut the animal to see how this pattern changes in each fragment as it begins to regenerate.

We then applied drugs or used RNA interference to target ion channels or gap junctions in individual cells and thus change the pattern of depolarization/hyperpolarization and cellular connectivity across the whole fragment.

As a result of the disruption of the bodys bioelectric circuits, the planarian regrows with two heads instead of one, or none at all.

When we re-cut the two-headed planarian in plain water, long after the initial drug has left the tissue, the new anatomy persists in subsequent rounds of regeneration.

Cells can clearly build structures that are different from their genomic-default anatomical outcomes. But are cells universal constructors? Could they make anything if only we knew how to motivate them to do it?

The most recent advances in the new field at the intersection of developmental biology and computer science are driven by synthetic living machines known as biobots. Built from multiple interacting cell populations, these engineered machines have applications in disease modeling and drug development, and as sensors that detect and respond to biological signals. We recently tested the plasticity of cells by evolving in silico designs with specific movement and behavior capabilities and used this information to sculpt self-organized growth of aggregated Xenopus skin and muscle cells. In a novel environmentin vitro, as opposed to inside a frog embryoswarms of genetically normal cells were able to reimagine their multicellular form. With minimal sculpting post self-assembly, these cells form Xenobots with structures, movements, and other behaviors quite different from what might be expected if one simply sequenced their genome and identified them as wildtype X. laevis.

These living creations are a powerful platform to assess and model the computations that these cell swarms use to determine what to build. Such insights will help us to understand evolvability of body forms, robustness, and the true relationship between genomes and anatomy, greatly potentiating the impact of genome editing tools and making genomics more predictive for large-scale phenotypes. Moreover, testing regimes of biochemical, biomechanical, and bioelectrical stimuli in these biobots will enable the discovery of optimal stimuli for use in regenerative therapies and bioengineered organ construction. Finally, learning to program highly competent individual builders (cells) toward group-level, goal-driven behaviors (complex anatomies) will significantly advance swarm robotics and help avoid catastrophes of unintended consequences during the inevitable deployment of large numbers of artificial agents with complex behaviors.

Understanding how cells and tissues make real-time anatomical decisions is central to achieving regenerative outcomes too complex for us to manage directly.

The emerging field ofsynthetic morphology emphasizes a conceptual point that has been embraced by computer scientists but thus far resisted by biologists: the hardware-software distinction. In the 1940s, to change a computers behavior, the operator had to literally move wires aroundin other words, she had to directly alter the hardware. The information technology revolution resulted from the realization that certain kinds of hardware are reprogrammable: drastic changes in function could be made at the software level, by changing inputs, not the hardware itself.

In molecular biomedicine, we are still focused largely on manipulating the cellular hardwarethe proteins that each cell can exploit. But evolution has ensured that cellular collectives use this versatile machinery to process information flexibly and implement a wide range of large-scale body shape outcomes. This is biologys software: the memory, plasticity, and reprogrammability of morphogenetic control networks.

The coming decades will be an extremely exciting time for multidisciplinary efforts in developmental physiology, robotics, and basal cognition to understand how individual cells merge together into a collective with global goals not belonging to any individual cell. This will drive the creation of new artificial intelligence platforms based not on copying brain architectures, but on the multiscale problem-solving capacities of cells and tissues. Conversely, the insights of cognitive neurobiology and computer science will give us a completely new window on the information processing and decision-making dynamics in cellular collectives that can very effectively be targeted for transformative regenerative therapies of complex organs.

Michael Levinis the director of the Allen Discovery Center at Tufts University and Associate Faculty at Harvard Universitys Wyss Institute. Email him atmichael.levin@tufts.edu. M.L. thanks Allen Center Deputy DirectorJoshua Finkelsteinfor suggestions on the drafts of this story.

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How Groups of Cells Cooperate to Build Organs and Organisms - The Scientist

SAN FRANCISCO and TAIPEI, Taiwan, Sept. 01, 2020 (GLOBE NEWSWIRE) -- Acepodia, a biotechnology company developing next generation solid tumor and blood-based cancer cell therapies, today announced key appointments to its business and clinical development teams. Mark J. Gilbert, M.D., a cell therapy pioneer, joins as senior vice president of Research and Development and will lead early-stage research efforts to advance the companys proprietary, potent and off-the-shelf cell therapies from exploratory development stages into clinical trials. Joseph S. McCracken, D.V.M., an industry veteran with over 25 years of experience in the biopharmaceutical industry, has been appointed as senior vice president of Business Development and will play a key role in driving strategic alliances and partnerships.

Dr. Gilberts decades of experience developing and managing successful oncology portfolios coupled with Dr. McCrackens extensive expertise in pharmaceutical business development operations will be essential for the near- and long-term growth of Acepodia, said Sonny Hsiao, Ph.D., chief executive officer of Acepodia. They are joining at a critical time for the company as we have recently entered clinical trials with our lead NK cell therapy in HER2 solid tumors and we continue to engage with global companies in the development and commercialization of next-generation cell therapies. We welcome them to the senior management team and look forward to their insight and leadership.

Dr. Gilbert added, Acepodias therapeutic approach to overcoming the challenges of treating solid tumors by arming its unique off-the-shelf platform with innovative tumor-targeting mechanisms is very promising. It represents an exciting potential breakthrough in the cell therapy treatment landscape. I look forward to working with the team to help realize this potential by advancing its revolutionary approach.

Dr. McCracken added, I am thrilled to join Acepodia at a pivotal time for the company and look forward to creating new synergies and strategic relationships that deliver value to the company, its partners and its stakeholders, while helping to advance its mission of delivering the next generation of effective cell therapies to patients.

Dr. Gilbert has decades of experience leading strategic drug development and portfolio management in medical oncology for several U.S. biotech and pharmaceutical companies. He was previously the chief medical officer of Juno Therapeutics, where he led the clinical development of its CAR-T cell therapy pipeline. Dr. Gilbert served as vice president and head of global clinical development, therapeutic area oncology at Bayer Schering Pharmaceuticals. Prior to Bayer Schering, he held several executive positions with Berlex Pharmaceuticals and its parent company Schering, AG, most recently as vice president and head of the global medical development group. Dr. Gilbert joined Berlex from Immunex, where his responsibilities included clinical development and medical affairs for Leukine and Mitoxantrone in hematology, oncology, Crohns disease, and multiple sclerosis. Dr. Gilbert received a B.S. in Biochemistry from the University of Iowa and his M.D. from the University of Iowa Medical School. He trained in internal medicine, infectious disease and medical oncology at the University of California, San Francisco, and the University of Washington, respectively. Prior to his executive positions in biotech and oncology companies, Dr. Gilbert was a faculty member at the Fred Hutchinson Cancer Research Center and the University of Washington and trained in the laboratory of Dr. Phil Greenberg, one of scientific co-founders of Juno Therapeutics.

Dr. McCracken has more than 25 years of experience in research, strategic business development and commercial roles in biotechnology and pharmaceutical companies. He was previously vice president and global head of business development and licensing for Roche Pharma, where he was responsible for Roche Pharmas global in-licensing and out-licensing activities. Prior to joining Roche Pharma, Dr. McCracken held the position of vice president of business development at Genentech for more than nine years, and previously held similar positions at Aventis Pharma and Rhone-Poulenc Rorer. Dr. McCracken holds a Bachelor of Science in Microbiology, a Master of Science in Pharmacology and a Doctor of Veterinary Medicine (D.V.M.) from The Ohio State University.

About Acepodia

Acepodia is a privately held biotechnology company focused on eradicating cancers of all types with potent and targeted first-in-class cell therapies. The companys next generation off-the-shelf natural killer (NK) cell therapies are based on a proprietary NK cell line (oNK) that has been selected for its potent anti-tumor activity. Acepodias flexible drug development platform is designed to supercharge oNK cells tumor affinity through both its chimeric antigen receptor technology and its unique ACC (Antibody-Cell Conjugation) technology that links tumor-targeting antibodies to the surface proteins of oNK cells. Its lead product candidate, ACE1702, is the first antibody-conjugated NK cell therapy in clinical development for the treatment of HER2-expressing solid tumors. For more information, visit https://www.acepodia.com.

Acepodia ContactSpike LoAcepodia886 (2) 2697-6100spike@acepodiabio.com

Investor ContactSylvia WheelerWheelhouse Life Science Advisorsswheeler@wheelhouselsa.com

Media ContactMichael Tattory LifeSci Communications1 (646) 751-4362mtattory@lifescicomms.com

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Acepodia Strengthens Management Team with Appointments of Biotech Industry Veterans - GlobeNewswire

DetailsCategory: AntibodiesPublished on Tuesday, 01 September 2020 10:48Hits: 174

Only PD-1/PD-L1 immunotherapy to demonstrate a significant survival benefit and improved response rate in combination with a choice of chemotherapies

LONDON, UK I September 01, 2020 I AstraZenecas Imfinzi (durvalumab) has been approved in the European Union for the 1st-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) in combination with a choice of chemotherapies, etoposide plus either carboplatin or cisplatin.

SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.1,2

The approval by the European Commission was based on positive results from the Phase III CASPIAN trial showing Imfinzi plus chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit for the 1st-line treatment of patients with ES-SCLC. It follows the recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency in July 2020.

Luis Paz-Ares MD, Ph.D., Chair, Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain and principal investigator in the Phase III CASPIAN trial said: For the first time, patients with extensive-stage small cell lung cancer in Europe will have the option of an immunotherapy combination with cisplatin, a preferred chemotherapy for many European physicians in this setting. Todays approval of Imfinzi provides physicians with an important new 1st-line treatment option that provides significant overall survival benefit with a well-tolerated treatment.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: Imfinzi plus chemotherapy is becoming a new global standard of care for patients with extensive-stage small cell lung cancer, and we are pleased to bring this option to patients in Europe who urgently need it. This is the first immunotherapy regimen to offer both a sustained survival benefit and an improved response rate, as well as a choice of chemotherapies and convenient dosing every four weeks during maintenance.

The CASPIAN trial met the primary endpoint of OS for Imfinzi plus chemotherapy in June 2019, reducing the risk of death by 27% versus chemotherapy alone (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.59-0.91; p=0.0047), with median OS of 13.0 months versus 10.3 months for chemotherapy alone. These results were published in The Lancet in 2019.3 Results also showed an increased confirmed objective response rate for Imfinzi plus chemotherapy (68% versus 58% for chemotherapy alone) and that Imfinzi added to chemotherapy delayed the time for disease symptoms to worsen.

An updated analysisrecentlyshowedsustained efficacy forImfinziplus chemotherapyafter a median followup of more than two years(OSHR: 0.75; 95%CI0.62-0.91; nominal p=0.0032), with median OS of 12.9 months versus 10.5 months for chemotherapy alone.The safety and tolerability forImfinziplus chemotherapy were consistent with the known safety profile of these medicines. No patients tested positive fortreatment-emergent anti-drug antibodies to Imfinzi.

The CASPIAN trial used a fixed dose ofImfinzi(1500mg) administered every three weeks for four cycles while in combination with chemotherapy and then every four weeks until disease progression.

Imfinzi in combination with etoposide and either carboplatin or cisplatin is also approved in the US, Japan and several other countries for the treatment of ES-SCLC in the 1st-line setting and is currently under regulatory review in other countries.

As part of a broad development programme, Imfinzi is also being tested following concurrent chemoradiation therapy in patients with limited-stage SCLC in the Phase III ADRIATIC trial.

Small cell lung cancer

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one fifth of all cancer deaths.4 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% classified as SCLC.5 About two thirds of SCLC patients are diagnosed with ES-SCLC, in which the cancer has spread widely through the lung or to other parts of the body.6 Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.6

CASPIAN

CASPIAN was a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared Imfinzi in combination with etoposide and either carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone. In the experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation. The trial was conducted in more than 200 centres across 23 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms. In June 2019, AstraZeneca announced the CASPIAN trial had met one primary endpoint of demonstrating OS forImfinziplus chemotherapy at a planned interim analysis. In March 2020, it was announced that the second experimental arm with tremelimumab did not meet its primary endpoint of OS.

Imfinzi

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on results from Phase III PACIFIC trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combinations including with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer, ovarian cancer, endometrial cancer and other solid tumours.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

An extensive Immuno-Oncology (IO) development programme focuses on lung cancer patients without a targetable genetic mutation, which represent up to three quarters of all patients with lung cancer.7 Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON and PEARL) and for patients in earlier stages of disease, including potentially-curative settings (Phase III trials MERMAID-1, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both as monotherapy and in combination with tremelimumab and/or chemotherapy.Imfinziis also in development in the Phase II trials NeoCOAST, COAST and HUDSON in combination with potential new medicines from the early-stage pipeline, includingEnhertu.

AstraZenecas approach to IO

IO is a therapeutic approach designed to stimulate the bodys immune system to attack tumours. The Companys IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZenecas Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients lives and the Companys future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visitastrazeneca.comand follow the Company on Twitter@AstraZeneca.

References

1. National Cancer Institute. NCI Dictionary Small Cell Lung Cancer. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer. Accessed July 2020.

2. Kalemkerian GP, et al. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? Journal of Oncology Practice, 2018:14;369-370.

3. Paz-Ares L, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. The Lancet. 2019;394(10212):1929-1939.

4. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed July 2020.

5. LUNGevity Foundation. Types of Lung Cancer. Available at https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed July 2020.

6. Cancer.Net. Lung Cancer - Small Cell. Available at https://www.cancer.net/cancer-types/33776/view-all. Accessed July 2020.

7. Pakkala, S, et al. Personalized therapy for lung cancer: striking a moving target. JCI Insight. 2018;3(15):e120858.

SOURCE: AstraZeneca

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Imfinzi approved in the EU for the treatment of extensive-stage small cell lung cancer | Antibodies | News Channels - PipelineReview.com

Sept. 1, 2020 12:05 UTC

~25-35 % survival over 5 years from diagnosis in vaccinated GBM patients vs a historical rate of ~ 5%

ROCKVILLE, Md. & SAN DIEGO--(BUSINESS WIRE)-- Immunomic TherapeuticsInc., (ITI), a privately-held clinical-stage biotechnology company pioneering the study of nucleic acid immunotherapy platforms, announced today that results from multiple ATTAC clinical studies of dendritic cell vaccines have been published online by American Association for Cancer Research (AACR) in an article titled, Once, Twice, Three Times a Finding: Reproducibility of Dendritic Cell Vaccine Trials Targeting Cytomegalovirus in Glioblastoma.

ITI is developing several dendritic cell vaccines for the treatment of cancer, including ITI-1000 for glioblastoma (GBM), with leaders in cancer immunotherapy for brain tumors, John Sampson, M.D., Ph.D. from Duke University and Duane Mitchell, M.D., Ph.D. from the University of Florida. ITIs dendritic cell vaccine is designed to target the pp65 viral antigen of Cytomegalovirus (CMV) that is expressed in GBM, but not in normal brain cells.

In the ATTAC studies, the GBM patients white blood cells are removed, matured into dendritic cells (DCs), and modified to generate a vaccine to the pp65 viral protein when fused to the LAMP1 protein for antigen presentation. This DC vaccine is then returned to the patient. As observed in the ATTAC studies, ITI believes this approach may harness the bodys immune system to recognize, attack and destroy tumor cells that express CMV in GBM and potentially other cancers. The published results from the three original ATTAC clinical studies are summarized below:

Three separate clinical trials conducted by Drs. Mitchell and Sampson utilized Cytomegalovirus specific dendritic cell vaccines in patients with newly diagnosed glioblastoma.

The three small studies (total n = 26; NCT#s 00639639, 2366728) revealed that overall 5-year survival increased from a historical low of 5% to 25%. However, in two of the studies, vaccination site pre-conditioning with either Td or GM-CSF:

This data is preliminary, and additional studies are needed.

These study results not only advance our understanding of a virus role in cancer, but they also signal tremendous hope to patients and their families suffering from this devastating disease, Sampson said. I look forward to continued evaluation of ITIs dendritic cell vaccines, including ITI-1000, in the ongoing, randomized, placebo-controlled ATTAC-II study.

GBM is the most aggressive form of brain cancer, often resulting in a patients death within one to two years from diagnosis. Historically, it is a very difficult disease to treat and current treatment options offer limited benefit to extend survival, added Mitchell. The results demonstrated with CMV-specific dendritic vaccines in the ATTAC studies are very encouraging, particularly in the observation of a significant fraction of long-term survivors and favorable safety profile of the vaccine platform. We remain steadfast in our pursuit to identify effective treatments for patients with GBM and look forward to the continued evaluation of ITIs vaccines in addressing this clear and pressing unmet medical need.

The AACR article can be found here.

About Glioblastoma (GBM)

According to the American Association of Neurological Surgeons, GBM is an aggressive brain cancer that often results in death within 15 months of diagnosis. GBM develops from glial cells (astrocytes and oligodendrocytes), grows rapidly, and commonly spreads into nearby brain tissue. GBM is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that GBM represents about 15% of all primary brain tumors and approximately 10,000 cases of GBM are diagnosed each year in the U.S.

About ITI-1000 and the Phase 2 (ATTAC-II) Study

ITI-1000 is an investigational dendritic cell vaccine therapy currently in a Phase 2 clinical trial (ATTAC-II) for the treatment of GBM. ITI-1000 was developed using Immunomics proprietary investigational lysosomal targeting technology, UNITE, in the context of cell therapy. In May 2017, Immunomic exclusively licensed a patent portfolio from Annias Immunotherapeutics for use in combination with UNITE and ITI-1000, allowing Immunomic to combine UNITE with a patented and proprietary CMV immunotherapy platform. The ATTAC-II study (NCT02465268) is a Phase II randomized, placebo-controlled clinical trial enrolling patients with newly diagnosed GBM that will explore whether dendritic cell (DC) vaccines, including ITI-1000, targeting the CMV antigen pp65 improves survival. This study is enrolling up to 120 subjects at 3 clinical sites in the United States. For more information on the ATTAC-II study, please visit http://www.clinicaltrials.gov.

About UNITE

ITIs investigational UNITE platform, or UNiversal Intracellular Targeted Expression, works by fusing pathogenic antigens with the Lysosomal Associated Membrane Protein 1, an endogenous protein in humans, for immune processing. In this way, ITIs vaccines (DNA or RNA) have the potential to utilize the bodys natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach puts UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. UNITE is currently being employed in a Phase II clinical trial as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP1 nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.

About Immunomic Therapeutics, Inc.

Immunomic Therapeutics, Inc. (ITI) is a privately-held, clinical stage biotechnology company pioneering the development of vaccines through its proprietary technology platform, UNiversal Intracellular Targeted Expression (UNITE), which is designed to utilize the bodys natural biochemistry to develop vaccines that generate broad immune responses. UNITE has a robust history of applications in various therapeutic areas, including infectious diseases, oncology, allergy and autoimmune diseases. ITI is primarily focused on applying the UNITE platform to oncology, where it could potentially have broad applications, including viral antigens, cancer antigens, neoantigens and antigen-derived antibodies as biologics. The Company has built a large pipeline from UNITE with six oncology programs and two allergy programs. ITI has entered into a significant allergy partnership with Astellas Pharma and has formed several academic collaborations with leading Immuno-oncology researchers at Fred Hutchinson Cancer Research Institute, Johns Hopkins University of Medicine, University of Florida, and Duke University. ITI maintains its headquarters in Rockville, Maryland. For more information, please visit http://www.immunomix.com.

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Immunomic Therapeutics Announces Publication of Results from 3 ATTAC Studies of CMV-Specific Dendritic Cell Vaccines for the Treatment of GBM -...

Despite many treatments for inflammatory bowel disease (IBD), a number of patients fail to respond long-term. In a new study, a team of researchers led by scientists at the University of California, San Diego (UCSD), School of Medicine, reported that the lasting nature of IBD may be due to a type of long-lived immune cell that can provoke persistent, damaging inflammation in the intestinal tract.

The research team integrated single-cell RNA and antigen receptor sequencing from immune cells isolated from samples taken from rectal biopsies or blood of IBD patients and healthy controls.They sought to elucidate key components, cellular states, and clonal relationships of the peripheral and gastrointestinal mucosal immune systems in health and ulcerative colitis (UC).

The work is published in the article, Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses, inScience Immunology.

We took advantage of a state-of-the-art approach allowing us to generate mRNA and antigen receptor sequencing data from the same single-cells, said Gene W. Yeo, PhD, professor of cellular and molecular medicine at UCSD School of Medicine, and analyzed thousands of individual cells, which is quite exciting.

It has long been believed that immune system dysfunction, in concert with genetic susceptibility and changes in the gut microbiome, plays a significant role in IBD. However, the types of immune cells involved and their specific contributions to IBD have remained unclear. CD8+ T cells are one component of the immune system that identify and kill cells infected by microbial pathogens.

When an infection has been conquered, the immune system leaves behind long-lasting cells called memory T cells, which reside in tissues or circulate through the body remembering past pathogens, ever ready to sound the alarm should specific invaders reappear.

The resulting single-cell sequencing resource revealed heterogeneity among tissue-resident memory T cells (TRM) in UC, with several subtypes of CD8+ tissue-resident memory T (TRM) cells, a specific class of memory cell that resides in organs once formed.

One of these TRMcell subtypes was distinguished by high levels of the transcription factor Eomesodermin and programmed to produce large amounts of cytokines and other molecules to kill newly detected infected cells. The downside is that excessive, persistently high levels of some cytokines can cause inflammation and tissue damage.

We found that this inflammatory TRMcell subtype seemed to be enriched in the intestinal tissues of patients with ulcerative colitis, a form of IBD that affects the colon, said John T. Chang, MD, professor of medicine at UCSD School of Medicine. Long-lived memory cells are a goal of vaccines, but this finding suggests that these same cells, coveted in the fight against infectious diseases, may actually be harmful in the context of IBD.

The researchers also found evidence that this inflammatory TRMcell subtype might not remain confined to intestinal tissue, but may also escape into the bloodstream.

This may explain why IBD can affect not just the intestines, but many other parts of the body as well, said Boland, a gastroenterologist at UCSD Health and assistant adjunct professor of medicine.

Taken together, the authors wrote that these results provide a detailed atlas of transcriptional changes occurring in adaptive immune cells in the context of UC and suggest a role for CD8+ TRM cells in IBD. They asserted that identifying this TRM population, and other disease-associated T and B cell subsets, provides a platform for future functional studies addressing how these subsets conspire to trigger chronic mucosal injury in UC.

Chang said the findings may help to explain why IBD is chronic and life-long, and point to the possibility of a remedy in the future: Targeting this inflammatory TRMcell subtype for elimination, thus ending the cycle of inflammation and tissue damage.

The researchers noted that much more work is needed to gain a deeper understanding of the role of tissue-resident memory T cells in IBD and to determine whether they can be targeted therapeutically.

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IBD Inflammation Linked to Long-Lived Immune Cell - Clinical OMICs News

As medical researchers rush to find a vaccine for Covid-19, the stories of earlier medical breakthroughs offer hope, but also reasons to be cautious about the timescale and effectiveness of any discovery.

In The Vaccine Race, Meredith Waldman describes how in the early 1960s scientists at Philadelphias Wistar Institute began working on a vaccine for rubella (German measles) using a controversial new method: germ-free cells from tissue extracted from an aborted foetus from a woman in Sweden. The Wistar cells were to revolutionise vaccine making, but ethical and political roadblocks meant it was 10 years before the institute was granted a patent, and it was not until 1978 that the Federal Drug Administration granted the pharmaceutical company Merck a licence for the vaccine in the US.

Waldmans book has uncanny parallels with the Rebecca Skloots The Immortal Life of Henrietta Lacks. This bestseller shows how the cervical cancer cells harvested in 1951 from an African American woman, Henrietta Lacks, gave rise to the immortal HeLa cell line. Lackss cells, which were taken without her consent, were instrumental in the development of the human papilloma virus (HPV) vaccine and other important therapies, but to this day Lackss family has not received compensation for her contribution to medical research.

Few breakthroughs can be more important than James Watson, Francis Crick and Maurice Wilkinss Nobel prize-winning discovery of the helical structure of DNA a story told in Watsons hugely popular but partial 1968 memoir The Double Helix. As Brenda Maddox explains in Rosalind Franklin: The Dark Lady of DNA, it was Franklins photograph of the molecule, shown to Watson without Franklins knowledge, that confirmed their intuition. Feminist scholars have sought to portray Franklin, who died in 1958 and who was overlooked for the 1962 Nobel prize, as the Sylvia Plath of molecular biology. However, in her remarkable book based on Franklins personal correspondence, Maddox shows Franklin maintained a close friendship with Watson and Crick until her death.

You may not have heard of monoclonal antibodies, or Mabs. But as Lara Marks explains in The Lock and Key of Medicine, these microscopic protein molecules, discovered in the mid-70s in the same Cambridge laboratory where Watson and Crick worked on DNA, quietly affect almost every aspect of our lives and have at least as great a claim to have revolutionised medicine. The applications of Mabs include organ transplantation, recombinant interferon and insulin, and personalised drug therapies such as Herceptin.

Generations of medical students have been inspired to go into research by Sinclair Lewiss 1925 novel Arrowsmith. Lewis teamed up with the science writer Paul de Kruif to write this tale of a small-town boy, Martin Arrowsmith, who rises to the pinnacle of medical science by discovering a phage therapy for plague. The prose is a little overwrought for modern tastes, but the novel was a runaway bestseller and is still worth reading for its account of the commercial pressures and professional rivalries endemic to science. Like his hero, who after treating plague on a remote Caribbean island turns down an offer to head up his old laboratory in New York, Lewis was averse to professional plaudits. In 1926 he declined the Pulitzer prize for fiction, claiming he had no desire to tickle the prejudices of a haphazard committee. A Nobel prize could be at stake for the discovery of a vaccine for Covid-19, but present-day medical researchers might wish to bear Lewiss scepticism in mind.

The Pandemic Century by Mark Honigsbaum is published by WH Allen (20). To order a copy go to guardianbookshop.com. Delivery charges may apply.

Continued here:
The best books about medical breakthroughs - The Guardian

Some taste cells are multitaskers that can detect bitter, sweet, umami and sour stimuli, a new study finds.

The research challenges conventional notions of how taste works. In the past, it was thought that taste cells were highly selective, capable of discerning only one or two types of the five basic stimuli only sweet, for instance, or only salty and sour. Though many cells are indeed specialists, the discovery of a subset of cells that can respond to up to four different tastes suggests that taste science is more complex than previously thought.

The study was published on Aug. 13 in the journal PLOS Genetics. The research was done on mice, which have a very similar taste system to humans, says Kathryn Medler, associate professor of biological sciences, College of Arts and Sciences, who led the study with first author Debarghya Dutta Banik.

This changes the way weve been thinking about how taste cells function and how taste information is collected in a taste bud and sent back to the brain, Medler says. Our data fills in a lot of holes. Other research has suggested that taste cells can be broadly responsive, but we were able to isolate individual taste cells and describe how they work. I cannot definitively state that humans have these broadly responsively taste cells, but based on the high degree of similarity between the mouse and human taste systems, I predict that these cells are very likely present in humans.

It is currently believed that taste cells are very specific about what stimuli they detect. The surprising thing with this new cell population is that individual cells can detect bitter, sweet, umami as well as sour stimuli, says Dutta Banik, a postdoctoral fellow in anatomy, cell biology and physiology in the Indiana University School of Medicine. Dutta Banik did the research while pursuing his doctorate at UB. It was surprising to know that individual taste cells can respond to so many taste qualities.

Taste cells are critical to survival: They help us decide whether a food is a good source of nutrients or a potential poison.

Beyond identifying the multitasking taste cells, the new study describes some of their traits. Scientists showed that the cells detect sour stimuli using one signaling pathway, and sweet, bitter and umami stimuli using a different pathway.

Experiments also showed that when broadly responsive taste cells are silenced, mice have trouble tasting sweet, bitter and umami stimuli. This was the case even when the more selective taste cells those that specialize in detecting individual stimuli remained active, says study co-author Ann-Marie Torregrossa, assistant professor of psychology, College of Arts and Sciences, and associate director of UBs Center for Ingestive Behavior Research.

We did a series of taste tests, says Torregrossa, who led the behavioral aspects of the study. When the animals were missing the function of either the broadly responsive cells or of the traditional taste cells, they responded to sweet, bitter and umami solutions as if they were water. This is very exciting because it suggests they needed both cells to taste the solution normally. When we did the same taste tests with animals that had both cells, they as you would expect licked the sweet solution avidly and avoided the bitter.

This shows that both of these cell populations are important for sending the taste information to the brain, Dutta Banik says.

The groundbreaking findings highlight how much scientists still have to learn about taste, including how taste buds work and send information to the brain.

Compared to other sensory systems, we know surprisingly little about how taste is coded and processed, Torregrossa says. This study identifies a new population of cells that are contributing to normal taste function, which could be a large piece in the puzzle.

The studys co-authors also included Eric D. Benfey, Amy R. Nelson, Zachary C. Ahart, Barrett T. Kemp and Bailey R. Kemp in the Department of Biological Sciences, and Laura E. Martin, Kristen E. Kay and Gregory C. Loney in the Department of Psychology. The research received support from the UB North Campus Imaging Facility, which is funded by the National Science Foundation.

More here:
New type of taste cell discovered in mice - University at Buffalo Reporter

Live Cell Imaging Market: Overview

Live cell imaging is the use of time lapse microscopy to study the living cells. The scientists use it to get a better understanding of the biological functions with the help of cellular dynamics. The live cell imaging technique is becoming increasingly popular in the healthcare industry.

The live cell imaging market can be categorized by products, by technologies, by end users and by regions. By product types, the live cell imaging market can be segmented into instruments, consumables and softwares. The instruments segment can be further sub-divided into standalone systems, cell analyzers, microscopes and image capturing devices. By technologies, the market can be segmented into fluorescence recovery after photobleaching (FRAP), fluorescence resonance energy transfer (FRET), high content screening (HCS), fluorescence in situ hybridization (FISH), ratiometric imaging, total iternal reflection fluorescence microscopy (TRIF), and multiphoton excitation microscopy (MPE) among others. Furthermore, the market can be segmented by applications into pharmaceutical industry, contract research organization, government and academic organization and diagnostic laboratories.

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Live Cell Imaging Market: Trends and Opportunities

The rising concern of cancer is one of the major factors behind the growth of increasing demand of this technology. Furthermore, the government is actively taking initiatives to fund cell based research. Moreover the live cell imaging has a wide area of application and it can used to understand dynamic processes and cellular structures. In addition, it can also be used to study cellular integrity, protein trafficking, enzyme activity, localization of molecules, exocytosis and endocytosis among others. Furthermore, the process can also be applied to monitor the molecules in live animals. Moreover, the pharmaceutical companies are increasingly using live cell imaging in research and development in order to develop new medicines. In addition, the live cell imaging is also used for high content screening.

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However, the cost of implementing live cell imaging is very high is acting as a restraint for the market. Moreover, the technology requires highly skilled professional in order to study and understand the cell functions. The lack of availability of skilled professional is also expected to restrain the growth of live cell imaging market. However, with increasing investments in training and development programs this factor is expected to have low impact in the long run. In addition, the live cell imaging technique is gradually being applied by pharmaceutical companies to develop personalized medicine. This demand is expected to grow in future.

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Live Cell Imaging Market: Geographical and Competitive Dynamics

By geography, the market can be divided into North America, Europe, Asia Pacific and Rest of the world. North America and Europe are the early adapters of technology. Furthermore, government initiatives are being taken in this region for research and development using live cell imaging. U.S. is the largest market for live cell imaging in North America. However, Asia Pacific region is expected to witness robust growth due to presence of developing nations such as India and China.The key players in the live cell imaging market are Sigma-Aldrich Corporation, Nikon Corporation, GE Healthcare, Carl Zeiss AG, Danaher Corporation, Olympus Corporation and Thermo Fisher Scientific, Inc., Molecular Devices, LLC, Becton, Dickinson and Company and Perkinelmer, Inc. among others.

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The report offers a comprehensive evaluation of the market. It does so via in-depth qualitative insights, historical data, and verifiable projections about market size. The projections featured in the report have been derived using proven research methodologies and assumptions. By doing so, the research report serves as a repository of analysis and information for every facet of the market, including but not limited to: Regional markets, technology, types, and applications.

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Live Cell Imaging Market: Rising concern of cancer is one of the major factors behind the market growth - BioSpace