The Department of Anatomy, Cell Biology & Physiology is dedicated to improving human health. The department houses cutting-edge biomedical research programs focused on a variety of diseases/disorders, trains the next generation of health care professionals through innovative educational programs and curricula, and participates in service initiatives that improve the teaching and research environment at Indiana University School of Medicine.

The department has a long history of synthesizing different subdisciplines of the life sciencesincluding cell and molecular biology, genetics, biophysics and physiology, anatomical structure, histology, neuroscience, and imagingto solve complex health problems from a basic science perspective.

The educational mission has provided foundational instruction in anatomy and physiology for tens of thousands of practicing physicians, physical therapists, physicians assistants and scientists working in academia, the biotech industry, private medical practice and governmental/nonprofit. The collective expertise of the departments diverse and collaborative faculty provide for a rich, technically advanced and interactive training experience for medical students and fellows.

Follow this link:
Anatomy Cell Biology and Physiology | IU School of Medicine

A microscopy technique created at UT Southwestern and powered by machine learning can detect multiple biochemical reactions in single cells in real time. The study found levels of the Xbp1 protein (green) rise in response to repeated or prolonged stress. Each colored hexagon corresponds to a different biochemical reaction tracked in the cells displayed in the center hexagon.

DALLAS Oct. 26, 2021 UT Southwestern researchers have identified a new mechanism by which stress causes cells to stop dividing.

Using techniques created at UT Southwestern, the team identified a protein in yeast that plays a previously unrecognized role in halting the cell cycle, the process by which one cell reproduces itself by splitting into two. After accumulating in response to stressful events, the Xbp1 protein appears to suppress the cell cycle, the study suggests.

The findings, published in the Journal of Cell Biology, appear to solve one long-standing mystery of the cell cycle. If scientists can identify a protein in mammals with a similar function, the research might eventually lead to new ways to accelerate wound healing by encouraging cell division or improve cancer treatment by doing the opposite.

Scientists have been studying this fundamental process for nearly seven decades, said Orlando Argello-Miranda, Ph.D., an Instructor who co-led the study with Assistant Professor Jungsik Noh, Ph.D., both of UTSWs Lyda Hill Department of Bioinformatics. Weve essentially identified a protein that can stop the cell cycle in response to stressful conditions.

Scientists have long known that the cell cycle consists of several defined stages as a cell goes from a resting state to increasing in size as it copies its genetic material or DNA in a process known as DNA replication, condenses its DNA, and finally divides into two daughter cells.

It has long been known that a stressful event such as starvation can send a cell into a protective state known as quiescence. Typically, the cell cycle halts just before DNA replication takes place, Dr. Argello-Miranda explained. However, a minority of cells seem to become quiescent at other points in the process.

To understand why, Dr. Argello-Miranda, Dr. Noh, and their colleagues studied yeast cells challenged by nutritional stress. The researchers were able to study individual cells in that state by using a technique called microfluidics six-color imaging developed at UT Southwestern. That technique combines a technology for cell culture called microfluidics with a six-color fluorescent-microscopy approach pioneered at UTSW in 2018. In microfluidics six-color-imaging, investigators pass cells through a tiny, fluid-filled chamber monitored with a specialized microscope and camera array. The researchers also used machine learning to track and detect up to six biochemical reactions in single cells in real time.

In previous studies in the field, researchers cultured yeast cells in flasks and were unable to track single cells, Dr. Argello-Miranda said. In contrast, we have obtained movies that record how individual cells stop dividing and enter quiescence.

Although most of the starved cells entered quiescence at the expected stage, right before DNA replication, about 7% paused at another stage of the cell cycle, he said.

Using the new techniques to tag and follow specific proteins in individual cells over time, the researchers found that all the starved cells showed elevated levels of a suite of stress response proteins. However, cells that became quiescent at unexpected points in the cell cycle all had an abundance of Xbp1, which the study found is needed to stop the cell cycle after DNA replication.

Further experiments showed that this accumulation of Xbp1 caused the cell cycle to pause, even when the activity of another protein called Cdk1 that encourages cell proliferation is high. A closer look showed that Xbp1 levels werent static rather, they climbed higher after each stressful event an individual cell experienced or the longer a stressful event lasted.

This accumulation was so predictable we could tell how many stressful events a cell had been exposed to by how much Xbp1 was present in the cell nucleus, Dr. Argello-Miranda said. The findings suggest that Xbp1 has a newly discovered function in regulating the cell cycle, allowing yeast cells to remember exposure to stress and to protect themselves by entering quiescence, he added.

Although there is no direct homolog to Xbp1 in mammals, other proteins seem to show similar biochemical activity in mammalian cells. Those proteins will be the subject of future research, he said.

This work was supported by grants from the Cancer Prevention and Research Institute of Texas (RP150596 and RR150058), The Welch Foundation (I-1919-20170325), and the National Institute of General Medical Sciences of the National Institutes of Health (K99GM135487).

Other UTSW researchers who contributed to this study include Ashley J. Marchand, Taylor Kennedy, and Marielle AX Russo.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

Visit link:
UTSW scientists identify protein that stops cell cycle in response to stress - UT Southwestern

Human interneuron progenitors derived from induced pluripotent stem cells (iPSCs) can be successfully transplanted and integrate into mouse brains, mature, and reverse signs of hippocampal network dysfunction associated with Alzheimer's disease, GABAeron scientists reported at ISSCR/JSRM.

Published: Oct. 27, 2021 at 7:00 AM CDT|Updated: 18 hours ago

SAN FRANCISCO, Oct. 27, 2021 /PRNewswire/ -- GABAeron, Inc. today presented promising preclinical data on their first-in-class, iPSC-based cell therapy product for Alzheimer's disease at the International Society for Stem Cell Research (ISSCR) and Japanese Society for Regenerative Medicine (JSRM) international meeting "Stem Cells: From Basic Science to Clinical Translation". The data, the first to be publicly shared since the company was founded in 2017, highlight the potential of transplanted, human iPSC-derived interneuron progenitors in treating Alzheimer's disease as well as other neurological disorders with interneuron deficit or loss.

GABAeron scientists successfully differentiated GABAergic interneuron progenitors from human iPSCs, and showed that when transplanted into the brains of an Alzheimer's disease mouse model carrying the major genetic risk factor apolipoprotein E4 (APOE4) the cells could mature, integrate into the hippocampus, and reverse signs of the hippocampal network dysfunction associated with Alzheimer's disease.

"We are incredibly excited by these data, which show the safety and efficacy of our novel iPSC-based approach in an Alzheimer's disease mouse model," said Robert W. Mahley, MD, PhD, chief executive officer and chief scientific officer of GABAeron. "Based on these results, we plan to continue our work to develop a cell replacement therapy to treat patients with APOE4-positive Alzheimer's disease."

Over the course of his career, Mahley president emeritus of the Gladstone Institutes and professor of pathology and medicine at the University of California, San Francisco has illuminated the importance and molecular details of the protein APOE. The gene for APOE comes in several versions and we now know that people with the APOE4 version of the gene have an increased risk of Alzheimer's disease and an earlier age of disease onset compared to people with the more common APOE3 version. Strikingly, APOE4 is associated with 6075% of all Alzheimer's disease cases.

GABAeron scientific co-founder Yadong Huang, MD, PhD, director of the Center for Translational Advancement at the Gladstone Institutes, San Francisco, discovered one important reason for the association between APOE4 and Alzheimer's disease. APOE4, his lab demonstrated, leads to the impairment and loss of hippocampal GABAergic interneurons cells critical for maintaining normal hippocampal activity, required for normal learning and memory, and damaged or lost in Alzheimer's disease brains.

"GABAeron was founded on the premise that if we can replace those interneurons via cell-based therapy, we can restore normal hippocampal activity and thus slow or reverse many of the memory and cognitive impairments associated with Alzheimer's disease," said Huang. "If this approach works, it will be a single treatment with long-lasting impact for Alzheimer'spatients."

In the new study, researchers led by Wen-Chin (Danny) Huang, PhD, and Iris Avellano, developed a novel effective method of coaxing human iPSCs carrying the APOE3 gene to differentiate into GABAergic interneuron progenitors. The resulting cells showed high viability, purity, and robust functionality with more than 90% committed to the correct developmental lineage.

A team led by Wan-Ying Hsieh, PhD, transplanted these interneuron progenitors into the hippocampus of 10-month-old mice carrying the human APOE4 gene; the interneuron progenitors showed robust survival and matured into functional GABAergic interneurons. At 7 months post-transplantation, more than half of the surviving cells had migrated out of the local area, populated the hippocampal subregions, and established connections with other existing neurons throughout the hippocampus.

"These exciting data reveal the high quality of human iPSC-derived interneuron progenitors generated at GABAeron and highlight the feasibility of their long-term survival and integration into mouse brains," said Hsieh. "Importantly, there was no tumor formation from the transplanted cells in over a hundred mice."

They next carried out electrophysiological recordings to study hippocampal network activity in the mice. As expected, the APOE4 mice had deficits in hippocampal activity that can underlie the memory impairments associated with Alzheimer's disease. Specifically, the mice had fewer sharp-wave ripples and their associated slow gamma power in the hippocampus both of which are critical for memory formation and retrieval. When each mouse was transplanted with approximately 120,000 iPSC-derived human interneuron progenitors carrying APOE3, these measurements of hippocampal activity both improved to the levels seen in healthy mice 7 months later.

"These results as a whole represent a critical step toward a potential interneuron-based therapy for APOE4-related Alzheimer's disease," said Qin Xu, PhD, senior director at GABAeron. "This builds up a solid foundation for our further work with clinical-grade human iPSCs."

GABAeron scientists are now adapting their culture techniques for the mass production of clinical-grade human iPSC-derived GABAergic interneuron progenitors. They are also working to identify the molecular characteristics of the mature GABAergic interneurons, which become successfully integrated into the hippocampus in the Alzheimer's disease mouse model.

"With this critical milestone reached, GABAeron will move forward, with great confidence, toward IND-enabling studies and future trials with clinical-grade human iPSC-derived interneuron progenitors for treating APOE4-related Alzheimer's disease," said Sheng Ding, PhD, scientific co-founder of GABAeron and a serial entrepreneur who co-founded two leading public companies, Fate Therapeutics (FATE) and Tenaya Therapeutics (TNYA). "We also plan to explore the usefulness of such a cell-based therapy for other neurological diseases with interneuron deficits or loss."

The ISSCR/JSRM international meeting "Stem Cells: From Basic Science to Clinical Translation" runs from October 2729, 2021 and is being held virtually this year.

About GABAeron

GABAeron, Inc. is a biopharmaceutical company founded in 2017, based on pioneer work initiated at the Gladstone Institutes, to build on the promise of combining precision medicine, regenerative medicine, and pharmaceutical intervention. The company is exploring a new first-in-class IND candidate to replace or restore neurons injured or lost in the brains of patients suffering from neurodegenerative and neurodevelopmental disorders.

For more information about GABAeron, please visit http://www.GABAeron.com.

View original content to download multimedia:

SOURCE GABAeron

The above press release was provided courtesy of PRNewswire. The views, opinions and statements in the press release are not endorsed by Gray Media Group nor do they necessarily state or reflect those of Gray Media Group, Inc.

Read the rest here:
GABAeron Presents Promising Preclinical Data on Stem Cell-Based Therapy for Alzheimer's Disease - WJHG-TV

Researchers around the world have tried many ways, and for many years, to generate neurons in the lab so they could study them better. Neurons-on-demand might also provide a therapeutic option for replacing neurons lost in neurodegenerative conditions, such as Parkinsons disease. In June 2020, University of California San Diego School of Medicine researchers announced a major step toward that goal: With one dose of a new proto-drug, they were able to turn other cell types directly into neurons, a feat that alleviated all Parkinsons disease symptoms in a mouse model.

Now, the UC San Diego-led team will receive a $9 million grant from the Aligning Science Across Parkinsons (ASAP) initiative to help advance this research and position it for the next phases of drug development. ASAP is a coordinated research initiative to advance targeted basic research for Parkinsons disease. Its mission is to accelerate the pace of discovery and inform the path to a cure through collaboration, research-enabling resources and data-sharing. The Michael J. Fox Foundation for Parkinsons Research is the implementation partner for ASAP and issuer of the grant, which contributes to the Campaign for UC San Diego.

Top: Mouse brain before treatment, with dopamine-producing neurons shown in green. Bottom: Mouse brain after PTB antisense oligonucleotide treatment, which converts brain support cells into dopamine-producing neurons (green).

Xiang-Dong Fu, PhD, Distinguished Professor of Cellular and Molecular Medicine is the lead investigator for the project, along with William C. Mobley, MD, PhD, Distinguished Professor of Neurosciences; and Bing Ren, PhD, and Steve Dowdy, PhD, both professors of cellular and molecular medicine at UC San Diego School of Medicine. The team also includes researchers from the Chinese Academy of Sciences.

This grant is supporting some of the most incredible progress being made in the Parkinsons sphere. Its a game-changing strategy that we hope will improve how Parkinsons is treated, said David Brenner, MD, vice chancellor of Health Sciences. We are grateful to ASAP for making these advancements possible.

The teams work centers on a protein called PTB, which is known for binding RNA and influencing which genes are turned on or off in a cell. Their previous studies showed that inhibiting the gene that encodes PTB transforms several types of mouse cells directly into new neurons in laboratory dishes.

To inhibit PTB in living organisms, the researchers developed a virus that carries an antisense oligonucleotide sequence an artificial piece of DNA designed to specifically bind the RNA coding for PTB, thus preventing it from being translated into a functional protein and instead stimulating neuron development. The virus infects brain cells, but cannot be transmitted from the injected mice to others.

The researchers have demonstrated that just a single treatment to inhibit PTB in mice converts native astrocytes, star-shaped support cells of the brain, into neurons that produce the neurotransmitter dopamine. Treatment restores normal dopamine levels in mice engineered to mimic Parkinsons disease. Physically, the mice recover motor function within three months after a single treatment, and remain free from Parkinsons disease symptoms for the rest of their lives.

Of course, mice arent people, and the animal model the team used doesnt perfectly recapitulate all essential features of Parkinsons disease. But the study provides an exciting proof of concept, they said.

With ASAPs support, the researchers will now be able to optimize their methods and test the methodology in other pre-clinical models. They have also patented the PTB antisense oligonucleotide treatment in order to move forward toward testing in clinical trials.

Parkinson's disease is a brain disorder that progressively worsens, leading to shaking, difficulty with coordination and struggles with walking and talking. The condition occurs when neurons in an area of the brain that controls movement slowly cease to function properly and die. Normally, these neurons produce a brain chemical called dopamine. When neurons become impaired, they produce less dopamine, which causes the movement problems indicative of the disease.

Although there is no current cure for Parkinson's disease, there are some medicines and surgical treatments that can relieve some symptoms, such as medications that increase dopamine levels or therapeutically affect other brain chemicals.

Private support, like the grant from ASAP, contributes to the Campaign for UC San Diego a university-wide comprehensive fundraising effort concluding in 2022. Alongside UC San Diegos philanthropic partners, the university is continuing its nontraditional path toward revolutionary ideas, unexpected answers, lifesaving discoveries and planet-changing impact. Learn more at Campaign for UC San Diego.

Continued here:
UC San Diego-Led Team Receives $9M to Advance Parkinson's Disease Treatments - UC San Diego Health

Collapsed femoral heads caused by osteonecrosisotherwise known as avascular necrosis unfortunately represent the root cause for approximately 10% of all hip replacements nationwide. Daniel Wiznia, MD, is utilizing a stem cell treatment at Yale School of Medicine and integrating new techniques along with 3D imaging technology as part of a joint-preservation procedure.

Occurring in more than 20,000 Americans each year, osteonecrosis of the femoral head is commonly diagnosed in patients in their 30s and 40s. The disease is caused by injury of the blood supply to the head of the femur, which is the ball portion of the hips ball and socket joint.

If unaddressed, this disease may ultimately lead to the collapse of the femoral head, requiring the patient to undergo a hip replacement. For patients in this age group, a total hip replacement is not ideal as it likely will wear out and the patient will require more surgery.

The goal for each case is clear: prevent the femoral head from collapsing and the need for a hip replacement. As part of a surgical procedure, Wiznia harvests bone marrow from the patients pelvis. The individuals own stem cells are then isolated from the marrow, concentrated, and injected into lesions within the avascular portion of the femura treatment that is only taking place at some of the nations largest medical centers.

The key in these instances is to discover the avascular necrosis before the head collapses, Wiznia said. Because the vascular injury is usually a painless event, patients are generally unaware of the specific point in time when the vascular injury occurred, which is why cases are rarely discovered in time. However, we do know that 80% of patients who have avascular necrosis on one side of the hip have it on the opposite side. We usually are able to catch that second asymptomatic side in those situations and conduct the core decompression with stem cell treatment before it collapses.

According to Wiznia, this treatment reduces the risk of the head of the femur from collapsing, and the stem cell therapy has shown promising results. Soon after the procedure, many patients with avascular necrosis experience rejuvenated blood supply to the area and the bone is repopulated with new cells. This can additionally alleviate the short-term need for a hip replacement.

This novel stem cell therapy has demonstrated improved pain and function, and the stem cells decrease the risk of the femoral head from collapsing, Wiznia said. This translates into fewer young patients requiring hip replacements, and subsequent surgeries in their later years.

As an engineer himself, Wiznia works closely with the Yale School of Engineering & Applied Sciences and the Integrated 3D Surgical Team to better tailor this treatment to each specific patient.

One of the challenges of orthopaedic surgery in the human body is that surgeons are operating in a three-dimensional space and are often reliant on two-dimensional imagery such as X-rays, Wiznia added. Through the use of computer modeling, we are able to customize those images and create models that are specific to each patient, which, in turn, enhances outcomes and overall post-operative success rates.

Enhanced models and 3D imaging enable surgeons like Wiznia to better locate and target both the lesions and necrotized bone in these instances. Effectively doing so regenerates the femoral head and stimulates new osteoblast growth, which will heal the region, maintain the integrity of the joint, and decrease the chance of femoral head collapse and need for a hip replacement.

Go here to see the original:
Stem Cells Used to Treat Avascular Necrosis of the Femoral Head - Yale School of Medicine

Use of comprehensive genomic profiling in patients with advanced nonsmall cell lung cancer (NSCLC) was linked with significant improvements in progression-free survival and overall survival.

Comprehensive genomic profiling (CGP) in the management of advanced nonsmall cell lung cancer (NSCLC) was shown to assist in matching patients with targeted therapies and clinical trials with those matched to these therapies associated with improved survival outcomes. Findings were published in BMC Medicine.

Despite the identification of several new targetable drivers in advanced NSCLC, the standard of care for these populations only includes genetic testing for EGFR, ALK, and ROS1 mutations. Notably, previous research shows use of the broader CGP profiling can better assess for emerging mutations, but research regarding its efficacy has not yet been determined.

Patients carrying alterations other than EGFR, ALK, and ROS1 now have increased access to targeted drugs off label or through a clinical protocol, said the study authors. Therefore, a re-evaluation on the clinical implications of CGP in the current treatment landscape of advanced NSCLC is warranted.

Seeking to further examine the clinical utility of CGP, they prospectively applied the approach to Chinese patients with advanced NSCLC registered in the Precision Medicine Project from October 2016 to October 2019 (N = 1564).

Efficacy of CGP in treatment selection was measured by the proportion of patients receiving a genomic profilingdirected, matched targeted therapy and the proportion of patients being enrolled into a biomarker-selected clinical trial directed by their profiling results.

Those provided with genotype-matched therapy were compared with those who were not matched for progression-free survival (PFS) and overall survival (OS).

In their findings, tumor genomic profiles were established in 1166 participants who underwent CGP:

Compared with patients with a nonmatched therapy, those who were given genotype-matched therapies showed significant improvements in PFS (9.0 vs 4.9 months; P < .001) and OS (3.9 vs 2.5 years; P < .001).

After excluding patients with standard targeted therapies, genomic profiling led to a matched targeted therapy in 16.7% (n = 24) and a matched trial enrollment in 11.2% (n = 16) of patients. Contrary to that found in the overall cohort, no PFS (4.7 vs 4.6 months; P = .530) or OS (1.9 vs 2.4 years; P = .238) benefit was observed with the use of genotype-matched targeted therapies in these populations.

In concluding, researchers said that given the low likelihood of benefit from the investigational or off-label use of targeted therapies, applicability of genomic profiling results should be taken with caution in patients without standard-of-care drugs.

Reference

Zhao S, Zhang Z, Zhan J, et al. Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer. BMC Med. Published online October 1, 2021. doi:10.1186/s12916-021-02089-z

View original post here:
Genomic Profiling Linked With Improved Patient Outcomes in Advanced NSCLC - AJMC.com Managed Markets Network

A recent report published in the journal Pharmacological Reviews from Utrecht University reviewed 200 studies revealing that high-quality nutrients in our food have a profound effect on our cells and, in particular, our immune system.

This study demonstrates that specific nutritional components can positively affect inflammatory responses and allergic reactions. To understand how this works it is important to have a basic understanding of the cell. In my opinion, the three key components of the cell are the nucleus which contains the genetic material, the mitochondria which are the fuel packs of the cell producing energy to maintain cell function and the little spoken about but vitally important membrane of the cell which is the interface between the external environment and the inner workings of the cell.

Some research suggests that the membrane is, in fact, the brain of the cell. On the surface of every cell are thousands of receptors which are basically doorways that allow external stimuli to affect different processes occurring within the cell.

There is no doubt that consuming 2 to 3 pieces of fruit and 3 to 5 servings of vegetables per day is a significant health practice that leads to low rates of heart disease and cancer. Tragically, less than 10% of our society practices healthy lifestyles, including the ingestion of the above amount of fruit and vegetables.

Our macronutrients are fat, protein and carbohydrates which basically form the fuel for cell metabolism and in the case of proteins the building blocks for all of our proteins and enzymes.

But, fruit and vegetables also contain a vast array of plant chemicals known as polyphenols, along with a variety of micronutrients which include vitamins, minerals and trace metals. The polyphenols, in particular, have a profound effect on the receptors on our cell surface and therefore maintain vital cell to cell communication and communication between external stimuli and the inner workings of the cell.

The study from Utrecht University demonstrates the vital importance of many of these high-quality natural nutrients in modulating the important processes that occur in our body and dampen down inflammation and allergy. Inflammation is a key component of the generation of our typical modern killers, such as cardiovascular disease, cancer, Alzheimers, Diabetes & respiratory disease which make up over 70% of the deaths around the globe on a yearly basis.

Pharmaceutical drugs work through a similar mechanism but because they are not natural chemicals may often damage many of these natural processes going on throughout our body.

As we age, the vast majority of people living in the modern world develop a variety of chronic complaints requiring pharmaceutical medications but the strong message from my work, reinforced by important trials studies such as this one from Utrecht University demonstrate clearly the value of the effects of high-quality nutrients on cell function.

Hippocrates knew this two and a half thousand years ago and it is somewhat sad that we see medical therapy as a pill or a procedure rather than the vital importance of leading a healthy lifestyle.

IMPORTANT LEGAL INFO This article is of a general nature and FYI only, because it doesnt take into account your personal health requirements or existing medical conditions. That means its not personalised health advice and shouldnt be relied upon as if it is. Before making a health-related decision, you should work out if the info is appropriate for your situation and get professional medical advice.

View original post here:
Food as medicine: how it works - Starts at 60

SAN FRANCISCO and SUZHOU, China, Oct. 27, 2021 /PRNewswire/ -- Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and NeoCura Bio-Medical Technology Co., Ltd. ("NeoCura"), a leading AI-enabled RNA precision medicine biotech company committed to building a global top RNA innovative drug platform, today jointly announced that they have entered into a strategic collaboration agreement to carry out a clinical study in China on the combination therapy of sintilimab from Innovent and individualized neoantigen vaccine NEO_PLIN2101 from NeoCura.

Innovent will collaborate with NeoCura in China to assess the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the combination therapy using sintilimab from Innovent and NEO_PLIN2101 from NeoCura in cancer patients, to advance the clinical development of combination immunotherapy for multiple solid tumors, and prepare to submit the Investigational New Drug (IND) application to the National Medical Products Administration (NMPA) in the near future.

Dr. Liu Yongjun, President of Innovent, stated: "We are impressed by NeoCura's differentiated R&D pipeline and international research team, and we are pleased to enter into this strategic collaboration to explore the clinical value of sintilimab in combination with neoantigen vaccines for solid tumors. Innovent has a robust pipeline with strong capabilities in immunology and cancer biology. Currently, we have five innovative drugs approved and launched in China and will have more than 10 innovative drugs to be launched in the next 2-3 years. Our fully integrated platform has accumulated strong R&D, clinical development and commercialization capabilities and is ideal for partners at home and abroad. We also hope to further explore the new opportunities in expanding indications and enhancing therapeutic efficacy of sintilimab in combination with novel therapies. We look forward to wider and in-depth collaboration between the two parties in the future. "

Dr. Wang Yi, founder of NeoCura, stated: "At present, neoantigen vaccines are a revolutionary emerging therapeutic approach worldwide. NeoCura has been focusing on the R&D of tumor neoantigen vaccines since its establishment, hoping to overcome the challenges of existing immunotherapy in the treatment of solid tumors through the application of new technologies. The collaboration with Innovent will play a synergistic role of personalized neoantigen vaccines and monoclonal antibody drugs and jointly explore the clinical effect of the combination therapy in the treatment of solid tumors, which is expected to improve the objective response rate of cancer immunotherapy and bring new opportunities for cancer combination regimens."

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

Additionally, Innovent currently has one regulatory submission under review in China for sintilimab, for the first line treatment of esophageal squamous cell carcinoma.

Additionally, four clinical studies of sintilimab have met their primary endpoints:

In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of non-squamous non-small cell lung cancer.

Sintilimab was included in China's National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

About NEO_PLIN2101

NEO_PLIN2101 is a personalized neoantigen vaccine developed by NeoCura, which can be custom made according to the unique tumor gene mutation of each patient. Through high-throughput sample sequencing and AI algorithm epitope prediction, high-quality neoantigen fragments that can be efficiently presented by tumor cells and elicit a potent immune responseare selected from patient's tumor sample. The mRNA vaccine encoded corresponding neoantigen is synthesized in vitro, vaccinated into patients to activate tumor-specific T cells to control tumor growth and reduce tumor burden. Compared to conventional approach, NEO_PLIN2101 has stronger specificity and immunogenicity that can induce anti-tumor immune response in cancer patients.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 26 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 5 products TYVYT (sintilimab injection), BYVASDA (bevacizumab biosimilar injection), SULINNO (adalimumab biosimilar injection), HALPRYZA (rituximab biosimilar injection) and Pemazyre (pemigatinib oral inhibitor) officially approved for marketing in China, 1 asset's NDA under NMPA review, sintilimab's Biologics License Application (BLA) acceptance in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 15 molecules in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: http://www.innoventbio.com. and http://www.linkedin.com/company/innovent-biologics/.

Note:

Sintilimab is not an approved product in the United States.

BYVASDA (bevacizumab biosimilar injection), HALPRYZA (rituximab biosimilar injection), and SULINNO (adalimumab biosimilar injection) are not approved products in the United States.

TYVYT (sintilimab injection, Innovent)

BYVASDA (bevacizumab biosimilar injection, Innovent)

HALPRYZA (rituximab biosimilar injection, Innovent)

SULINNO (adalimumab biosimilar injection, Innovent)

Pemazyre (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

Disclaimer:

1. This indication hasn't been approved in China. 2. Innovent does not recommend any off-label usage.3. For medical and healthcare professionals only.

About NeoCura

Founded in 2017, NeoCura is committed to building a global top RNA innovative drug platform. NeoCura has built a multi-omics data collection platform and corresponding omics database, empowered by AI and bioinformatics technology for target deep mining and automated drug design for innovative RNA medicine research and development, and built a leading RNA drug manufacturing center in China to support pipeline research and development as well as clinical needs.

NeoCura brings together the world's top scientists, senior industry experts and international first-class academic consultant teams. The core R&D team includes dozens of doctoral/postdoctoral fellows from prestigious schools such as Harvard, Cambridge, Cornell, Peking University, Tsinghua University and Chinese Academy of Sciences. The professional fields cover multiple disciplines including genomics sequencing, AI algorithm, bioinformatics, onco-immunology, vaccine design and drug delivery. Team members have held core R&D positions in top international research institutions or enterprises such as Harvard Medical School, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston Children's Hospital, and the research results have been published on hundreds of articles in international high-portfolio journals such as Nature, Science, and Cell.

NeoCura has independently developed AI bioinformatics platform for deep target mining, RNA medicine platform, automated drug design platform, multi-omics big data collection and analysis platform and target validation platform, aiming to promote RNA drug clinical research in combination with artificial intelligence algorithm plus real-world data validation. Its proprietary NeoCuraTM AI ALPINE tumor neoantigen prediction algorithm has the highest prediction accuracy in the world. Relying on its own R&D expertise and technical advantages, NeoCura has carried out in-depth studies in the tumor neoantigen vaccine, tumor microenvironment modulations, etc., developed personalized neoantigen vaccine for different individuals, established a public neoantigen pool for the high incidence of cancers in China, significantly reduced the cost of neoantigen drug treatment and shortened the preparation cycle. At present, NeoCura has jointly carried out clinical trials with many leading hospitals and will become a new landmark in the field of cancer treatment. With its cutting-edge AI technologies, outstanding innovation capability and robust oncology pipelines, NeoCura is recognized as one of the Most Promising Enterprise in China and Top 10 China AI/Algorithm Pharmaceutical Innovative Enterprise in 2021.

Company website: http://www.neocura.com.cn.

Innovent Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

SOURCE Innovent Biologics

Follow this link:
Innovent and NeoCura Announce Strategic Collaboration to Study the Combination Therapy of Sintilimab and Neoantigen Vaccine NEO_PLIN2101 for Cancer...

Collaboration supports precision medicine approach to autoimmune diseases by targeting metabolic hubs to enable target identification, biomarker discovery and patient stratification

CAMBRIDGE, Mass. & MARSEILLE, France, October 27, 2021--(BUSINESS WIRE)--Rheos Medicines, a biopharmaceutical company bringing molecular targeting and precision treatment to autoimmune and inflammatory disease, today announced a research collaboration with the French non-profit research organization CRYOSTEM. The goal of the research collaboration is to provide biological resources from HSCT (Hematopoietic Stem Cell Transplantation) patients in order to evaluate MALT1-targeted therapeutics, including Rheoss lead product candidate, RHX-317, for Graft-versus-Host Disease (GvHD), based on functional immunologic profiling of patients and identification of molecular signatures for MALT1 activity. This collaboration supports a precision medicine approach to enable the treatment of GvHD, by defining the predominant metabolic pathways in the anabolic hub that drive key pathogenic pathways in GvHD patient subsets.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20211027005366/en/

"CRYOSTEM chose to establish this collaborative research program with Rheos because it aligns with our mission to promote our collection of biological resources to help scientists accelerate innovation and extract new knowledge to allow better prevention, diagnosis and treatment of GvHD as one of the HSCT major complications that is a barrier to effective stem cell transplants for patients," said Professor Rgis PEFFAULT de LATOUR, co-founder and scientific coordinator of CRYOSTEM.

The research program brings together the collaborators two domains of expertise to address the challenge of treating GvHD, a major cause of post-transplant morbidity and mortality in patients who undergo allogeneic HSCT. With its proprietary technology platform, Rheos brings insights from studies showing that MALT1 activity underpins the activation of multiple cell types and signaling pathways within a metabolic hub that is dysregulated in GvHD, as well as approaches to predict and stratify patient response to treatment. CRYOSTEM operates through a national biobanking network bringing together transplant units and Biological Resources Centers to accelerate research in the area of complications of HSCT, housing the first and unique collection in Europe dedicated to HSCT complications. This collection of approximately 200,000 biological samples, taken from patients before and after transplant, support research projects that meet rigorous selection criteria by a world-renowned scientific committee.

Story continues

"This research collaboration with the world-class experts at CRYOSTEM will enable us to significantly build on our existing work in immune cells from healthy donors, and now study GvHD patient samples to evaluate the effect of inhibiting a key drug target on the activation state of multiple immune cells and the specific pathways that are dysregulated in GvHD," said Dania Rabah, Ph.D., Chief Scientific Officer of Rheos Medicines. "We believe the data generated under this collaboration can validate our precision medicine approach to identify novel patient subsets in autoimmune and inflammatory diseases, while also informing the clinical development plan for RHX-317, our novel MALT1 inhibitor drug candidate to treat GvHD."

Under the terms of the research collaboration, CRYOSTEM will provide Rheos with biological resources for post-transplant patients in three categories: those who developed acute GvHD, those who developed chronic GVHD, and those who did not develop GvHD. Rheos will evaluate therapeutic targets for GvHD through these study methods:

Measure the effectiveness of MALT1 inhibition against disease-relevant functions of immune cells, comparing results across the three different categories of patient samples to determine sensitivity of MALT1 inhibitor drug response and target validation in chronic GvHD.

Perform multi-omic analyses of patient samples to define signatures reflecting MALT1 therapeutic activity.

Upon successful completion of these initial studies, both parties may agree to expand the research to include larger GvHD patient cohorts and additional evaluation of patient subsets to predict therapeutic response for a potential precision medicine approach to GvHD.

"As with many diseases that have an aberrant immune response, todays treatments for GvHD involve broad immunosuppression, and we lack molecularly-targeted medicines that target disease pathways," said Robert Zeiser, M.D., Head of Tumor Immunology and Immune Modulation and professor at the University of Freiburg Medical Center in Germany. "Rheoss therapeutic approach to target MALT1 for the treatment of GvHD is built on compelling findings that MALT1 activates cellular activity and signaling pathways that are dysregulated in GvHD. I look forward to continued progress with this MALT1 inhibitor that offers a promising new approach for patients with GvHD."

About MALT1

MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a dual-function scaffolding molecule and paracaspase that is expressed preferentially in immune cells. In addition to its role in NF-B mediated lymphocyte activation and proliferation, Rheos has shown that MALT1 activity is central to the anabolic shift that fuels pathogenic functions of immune cells. Inhibiting MALT1 attenuates the activity of multiple immune cell types simultaneously to dampen the inflammatory response in the activated immune system. Because of its role in cellular metabolism, the effects of MALT1 inhibition can be monitored by metabolite signatures, opening an opportunity to monitor disease and evaluate activity of therapeutics in patients and patient subsets.

About CRYOSTEM

CRYOSTEM was initiated in 2010, under the aegis of the SFGM-TC (Socit Francophone de Greffe de Moelle et de Thrapie Cellulaire (https://www.sfgm-tc.com/) to create a multicenter biobank in the field of HSCT. After initially concentrating on Graft-versus-Host Disease (GvHD), CRYOSTEM has broadened its focus to all HSCT complications. Thanks to its network of all the transplant units in France and 28 Biological Resources Centers, CRYOSTEM has established a standardized collection of high-quality biological samples associated with well-annotated clinical data from donors and patients pre- and post-HSCT. Currently, the collection has reached approximately 200,000 available samples coming from nearly 5,900 patients. Since 2015, CRYOSTEM has provided the national and international scientific community with these samples for large-scale research to improve the knowledge of HSCT complications. CRYOSTEM has been funded by the French governments "National Investment Program" and has also received financial support from the French National Cancer Institute (INCa) and patient associations. For more information, please visit http://www.cryostem.org.

About Rheos Medicines

Rheos Medicines is a biopharmaceutical company developing novel, small molecule medicines to treat autoimmune and inflammatory diseases with greater precision by targeting the metabolic hubs of the immune system. Using our proprietary MetPM platform, the Rheos team integrates an unmatched knowledge base of immunometabolism networks based on bioinformatic integration of genetic, transcriptomic, epigenomic and metabolomic datasets, including from patient data and samples. We have built a pipeline of novel, differentiated drug programs to address autoimmune and inflammatory diseases by targeting fundamental underpinnings of immune system dysfunction while, at the same time, identifying the molecular signatures for patient stratification and selection. Rheos has assembled leading scientists whose discoveries opened the field of immunometabolism, clinicians with a deep understanding of immune-mediated diseases, and an experienced biotech leadership team. Rheos was founded by Third Rock Ventures and is located in Cambridge, MA. For more information, please visit http://www.rheosrx.com. We invite you to follow us on LinkedIn and @Rheosrx.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211027005366/en/

Contacts

FOR RHEOS MEDICINES:

Media: Kathryn MorrisThe Yates Network LLC914-204-6412kathryn@theyatesnetwork.com

Investor: Hannah DeresiewiczStern Investor Relations, Inc.212-362-1200hannah.deresiewicz@sternir.com

FOR CRYOSTEM:

Media: Jean-Mehdi GrangeonKOM AgencyMarseille, Franceinfo@kom-fr.com

Partnership: Emilie RobertAssociation CRYOSTEMMarseille, Franceemilie.robert@cryostem.org

See the rest here:
Rheos Medicines Forms Research Collaboration With CRYOSTEM to Evaluate MALT1Targeted Therapeutics for Graft-versus-Host-Disease - Yahoo Finance

Writing in EMBO reports, researchers at University of California San Diego School of Medicine and Moores Cancer Center at UC San Diego Health describe how a pair of fundamental genetic and cellular processes are exploited by cancer cells to promote tumor survival and growth.

The findings appear in the October 26, 2021 issue of the journal, a publication of the European Molecular Biology Organization.

Cancer is driven by multiple types of genetic alterations, including DNA mutations and copy number alterations ranging in scale from small insertions and deletions to whole genome duplication events.

A stained histological slide, magnified 100 times, depicts cancer cells expansively spread through normal breast tissues, including a duct completely filled with tumor cells. Credit: Dr. Cecil Fox, National Cancer Institute

Collectively, somatic copy number alterations in tumors frequently result in an abnormal number of chromosomes, termed aneuploidy, which has been shown to promote tumor development by increasing genetic diversity, instability and evolution. Approximately 90 percent of solid tumors and half of blood cancers present some form of aneuploidy, which is associated with tumor progression and poor prognoses.

In recent years, it has become apparent that cells cohabiting within a tumor microenvironment are subject not only to external stressors (mainly of metabolic origin, such as lack of nutrients), but also to the internal stressor aneuploidy. Both activate a stress response mechanism called the unfolded protein response (UPR), which leads to an accumulation of misfolded proteins in the endoplasmic reticulum (ER) of cells an organelle that synthesizes proteins and transports them outside the cell.

When this primary transport/export system is disrupted, UPR attempts to restore normal function by halting the accumulation of misfolded proteins, degrading and removing them and activating signaling pathways to promote proper protein folding.

If homeostasis or equilibrium is not re-established quickly, non-tumor cells undergo cell death. Conversely, cancer cells thrive in this chaos, establishing a higher tolerance threshold that favors their survival.

In these circumstances, they also co-opt neighboring cells in a spiral of deceit that progressively impairs local immune cells, said co-senior author Maurizio Zanetti, MD, professor of medicine at UC San Diego School of Medicine and a tumor immunologist at Moores Cancer Center with Hannah Carter, PhD, associate professor of medicine and a computational biologist. Zanetti had previously introduced the hypothesis in a Science commentary.

The researchers hypothesized that aneuploidy, UPR and immune cell dysregulation could be linked together in a deadly triangle. In the new study, Zanetti, Carter and colleagues analyzed 9,375 human tumor samples and found that cancer cell aneuploidy intersects preferentially with certain branches of the signaling response to stress and that this finding correlates with the damaging effects of aneuploidy on T lymphocytes, a type of immune cell.

This was an ambitious goal not attempted before, said Zanetti. It was like interrogating three chief systems together chromosomal abnormalities in toto, signaling mechanisms in response to endogenous stress and dysregulation of neighboring immune cells just to prove a bold hypothesis.

We knew the task would be challenging, added Carter, and that we would need to create and refine new analytical tools to test our hypotheses in heterogeneous human tumor data, but it was a worthwhile risk to take.

The findings, they said, show that the stress response in cancer cells serves as an unpredicted link between aneuploidy and immune cells to diminish immune competence and anti-tumor effects. It also demonstrates that molecules released by aneuploid cells affect another type of immune cells macrophages by subverting their normal function to turn them into tumor-promoting actors.

The findings offer new opportunities to understand tumor progression as a balance between the progressive accumulation of chromosomal abnormalities during tumor evolution and the progressive decay of anti-tumor immunity, said the authors, with the signaling response to stress gauging and regulating the relationship.

In practical terms, they said, a new aneuploidy score defining the burden of chromosomal abnormalities, developed for the study, could set a new paradigm for assessing the biological stage of tumor progression in patients and be used to extrapolate immune status.

It may also inform on new opportunities for pharmacological or genetic interventions that interfere with specific branches of the UPR as the mediator of aneuploidy-driven local immune dysregulation. This non-immunological approach could make immunotherapy of cancer more efficient, said Zanetti.

Co-authors include: Su Xian, Magalie Dosset, Gonzalo Almanza, Stephen Searles, Paras Sahani, T. Cameron Waller, Kristen Jepsen and Hannah Carter, all at UC San Diego.

Funding for this research came, in part, from the National Institutes of Health (grant RO1 CA220009), Mark Foundation Emerging Leader Award and the National Cancer Institute (grant T32CA121938).

Continue reading here:
Tumor Reasons Why Cancers Thrive in Chromosomal Chaos - UC San Diego Health