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The Lab Report: Sharma Lab studies biodiversity of arachnids – The Badger Herald

Posted: September 16, 2022 at 2:36 am

The Sharma Lab at the University of Wisconsin Department of Integrative Biology uses evolutionary biology to discover new species and study the molecular basis for biodiversity. This work allows researchers to pinpoint the exact genes that cause dramatic physical differences between species.

Headed by Integrative Biology Department associate professor and principal investigator Prashant Sharma, the lab aims to further understand the evolutionary relationship between scorpions, spiders and other arachnids, and how that compares to other groups of animals.

According to the Sharma Lab website,the project analyzes the specimens genomes and constructs a phylogenetic tree a visual representation of how species are related. This complete arachnid phylogeny is an important tool for researchers to understand how mutation results in new species and help classify species discovered in the future.

The findings of this study are relevant to more than just arachnids Sharma said any small discovery in biodiversity is a victory for the entire integrative biology field.

[This lab] focuses on what biodiversity looks like and how its maintained on the molecular level the specific gene products that cause these different phenotypes and how they affect our broader understanding, Sharma said. We dont really know what species are important to prioritize for conservation, we dont know whats important to save, if we dont know whats out there. Thats why this research is so important.

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While evolutionary biology is an extensive field, many students have very little experience with it, as was the case for undergraduate Hugh Steiner, who has worked in the Sharma Lab for a year and a half. Steiner said he was inspired to pursue research in the lab after having Sharma as a professor, igniting his interest in evolutionary biology and molecular phylogenetics. In the future, Steiner said he would like to continue this line of research, which he never considered before meeting Sharma.

Within Sharmas lab, Steiner applies molecular phylogenetic techniques to identify and classify new species of blind cave spiders taken from 44 cave sites throughout the Levant a large area in the eastern Mediterranean, including Israel, Palestine and Syria. Despite many of these species being physically indistinguishable to the naked eye, Steiner used molecular data to prove the species are in fact new and separate.

After his work on the species discovery project, Steiner said he shifted his focus from the more computational side of research to molecular experiments.

I decided to try my hand at evolutionary development research instead of just taxonomy, Steiner said. Theres an entirely different set of research techniques we use in the lab that Ive barely even explored yet.

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Evolutionary development, another facet of the Sharma Labs research, uses genetic data to identify the exact genes that cause differences between species, working backwards to identify new targets for research, according to BioMed Central. Once promising genes are identified, researchers categorize the function by removing the gene product and observing the changes in appearance and behavior. Researchers can simulate evolution by identifying which specific genes in arachnids cause visible differences between closely-related species.

The Sharma Lab has also begun genetic analysis to scorpions by using machine learning to predict which scorpion species venoms may be medically relevant. Lab members then analyze these gene products and test venoms for antibacterial or even tumor-reducing properties, said Sharma.

According to Sharma, new antibiotics that may be discovered using this research are of particular interest because bacteria adapt to frequently-used antibiotics, leading to anti-bacterial resistance. Any new antibiotic discovered will give doctors new tools to combat infections.

We know that some of these venoms have therapeutic properties, but its a scavenger hunt to see which are which, Sharma said. [Artificial intelligence] allows us to link [genetic] sequences of known venoms with available functional data to predict what peptides contained in arachnid genomes are promising.

Evolutionary biology involves analysis of massive data sets, with each species genome containing billions of base pairs, according to Sharma. Even a small sample size is too large for a human to analyze by hand. Combining existing understanding of genetics and molecular physiology with the unparalleled processing power of artificial intelligence has completely changed the field of evolutionary biology.

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Sharma said machine learning has facilitated much of his recent research. In turn, each biological discovery gives future programs additional data to use, further honing their research techniques.

We dont know whats important if we dont know whats out there, Sharma said. Using these computational tools, were answering questions that couldnt even be asked 20 years ago we are in the middle of a revolution not just in [biological research] but also in how we ask these questions.

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Environmental Scientist Jesse Ausubel to Receive 2022 Nierenberg Prize for Science in the Public Interest – Scripps Institution of Oceanography

Posted: September 16, 2022 at 2:36 am

Renowned environmental scientist Jesse H. Ausubel will be honored with the 2022 Nierenberg Prize for Science in the Public Interest. This award is presented annually by Scripps Institution of Oceanography at UC San Diego and the Nierenberg Family to honor the memory of William A. Nierenberg, an esteemed physicist and national science leader who served Scripps Oceanography as director for two decades.

The public is invited to attend the 2022 Nierenberg Prize ceremony and a presentation from Ausubel in a free event on Oct. 13 at 6 p.m. at the Robert Paine Scripps Forum for Science, Society and the Environment on the Scripps campus. RSVP here.

His presentation, Peak human? Thoughts on the evolution of the enhancement of human performance, will examine whether the human species can continue to improvemuch like cars, computers, or other technologyor whether our species has reached its peak.

In a career spanning more than four decades, Ausubel has conceived, developed, and led numerous projects to observe and better understand the environment. This includes high-profile work on several major programs to survey and catalog the planets biodiversity. In 2000, he and marine biologist Frederick Grassle of Rutgers University initiated the decade-long Census of Marine Life, an international program nurtured by the Alfred P. Sloan Foundation that assessed and explained the diversity, distribution, and abundance of life in the oceans. In 2002, Ausubel and Canadian ecologist Paul Hebert began the International Barcode of Life initiative, which provides short DNA sequences to efficiently identify all species of animals, plants, and fungi. Starting in 2006, he led the inception of the Encyclopedia of Life, a freely available online resource that aims to develop a web page for every species.

The esteemed scientist was notified about his selection to receive the 2022 Nierenberg Prize in a letter from Scripps Director Margaret Leinen. Of this Ausubel wrote, Dr. Leinens letter about the Nierenberg Prize dazed me with thoughts about the luster of past awardees and the fun to follow as well as the gravity of the subject of science and society.

Ausubel currently serves as director of the Program for the Human Environment at The Rockefeller University in New York City. The program leads research on long-term trends relevant to the environment with a goal of harnessing technology to lighten the human footprint, spare land for nature, and restore the oceans. He has also served as an executive of the Alfred P. Sloan and Richard Lounsbery foundations, program director of the National Academies, and long-term research affiliate of the Woods Hole Oceanographic Institution.

Ausubel began his career working for the U.S. National Academy of Sciences (NAS) and National Academy of Engineering (NAE) in Washington, D.C., starting with a 1977 Sloan Foundation fellowship. Shortly after, Ausubel was a main organizer of the first UN World Climate Conference in Geneva in 1979, an event which elevated global warming on scientific and political agendas and led to the creation of the World Climate Program, much of which Ausubel drafted.

In the decades that followed, Ausubel published research on climate impacts and adaptations and decarbonization, and in 1983 helped initiate the International Geosphere-Biosphere Program to understand the causes and outlook for global change. In 1991, with physicist Robert Frosch and others he originated the field of industrial ecology, the study of the network of all industrial processes as they may interact and live off each other and create opportunities for waste reduction and dematerialization.

More recently, Ausubel initiated the Deep Carbon Observatory to search for the origins and limits of life and the roots of petroleum and natural gas, and he launched the International Quiet Ocean Experiment to improve knowledge of ocean soundscapes and assess how human activities affect marine life. His group at The Rockefeller now explores how loose DNA in seawater (or eDNA) can improve knowledge of the kinds and amounts of life nearby.

The Nierenberg Prize holds significance for Ausubel as he had a personal connection with Dr. Nierenberg. The two first met in 1977 at the founding meeting of the Climate Research Board of the National Academies, where Ausubel served as a resident fellow. Ausubel also worked for Nierenberg in the 1980s, in Nierenbergs capacities as chair of the Carbon Dioxide Assessment Committee of the Academies and the Committee on International Science of the National Science Board, the governing body of the National Science Foundation.

Recalling his experience working with and being mentored by Nierenberg, Ausubel wrote, William Nierenberg liked risky activities that might have a high payoff. He believed society expected science to accomplish the incredible, like finding and recovering a submarine lost in the vast, deep Pacific. He encouraged me to take some of the most fruitful chances of my career, including initiating the Census of Marine Life.

The Nierenberg Family said they were pleased the selection committee put forth Ausubel as the 2022 recipient of the Nierenberg Prize for Science in the Public Interest.

Jesse and our father shared numerous scientific projects together, and had many broad conversations about the wonders of the physical, biological and cultural world, said Vicki Tschinkel, William Nierenbergs daughter. Jesse is renowned for creating colossal collaborations to answer diverse mega questions ranging from climate change to the Census of Marine Life to investigating the source of Leonardo DaVincis talent. His strength, brilliance and good nature invite participation and debate from all.

Ausubel helped found and foster several organizations, including the Partnership for Observation of the Global Oceans (POGO) and the Andrew W. Marshall Foundation. He is the recipient of numerous awards and honors for his environmental research, including the Blue Frontier/Peter Benchley prize for ocean science; membership in the American Academy of Arts and Sciences; and Japans International Cosmos Prize, which he shared with other leaders of the Census of Marine Life project. In the spring of 2021, the website Academic Influence ranked Ausubel as the worlds tenth most influential earth scientist.

Beyond environmental research, Ausubel has helped spur biology in art and the art/bio movement, which uses new tools in molecular biology, genetics, and microbiology for discovery in art history and for the conservation of cultural heritage.

The Nierenberg Prize, which includes a bronze medal and $25,000, is awarded for outstanding contributions to science in the public interest. Previous awardees include atmospheric scientist Warren Washington, biochemist and Nobel Prize winner Jennifer Doudna, filmmaker Sir David Attenborough, and primatologist Dame Jane Goodall, among others.

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Environmental Scientist Jesse Ausubel to Receive 2022 Nierenberg Prize for Science in the Public Interest - Scripps Institution of Oceanography

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Dayton Therapeutics Discovers New Therapeutic Uses of Satraplatin for Treatment of Rare Lymphomas – StreetInsider.com

Posted: September 16, 2022 at 2:36 am

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Zug, Switzerland--(Newsfile Corp. - September 14, 2022) - Dayton Therapeutics has announced that the company is using its AI-powered genetic and molecular research model for investigating new therapeutic uses of clinical stage drug candidates where development has been discontinued - in particular satraplatin. Satraplatin is an antineoplastic agent derived from platinum that was previously investigated for use in the treatment of patients with advanced prostate cancer. Dayton Therapeutics is now investigating development of satraplatin for the treatment of rare lymphomas and as an outcome of the research that Dayton Therapeutics has conducted, the company has already filed two patent applications for strong IP protection. The firm's stated goal is to launch satraplatin by 2026, and revenues could potentially reach almost half a billion US Dollars.

Intravenous platinum drugs are among the most widely used drugs for cancer treatment today. As the first orally active platinum-based chemotherapeutic drug in the world, satraplatin underwent extensive clinical development and trials for the treatment of prostate cancer. It was first mentioned in medical literature in 1993 as a drug that offered great potential in this regard. Nevertheless, in 2007, GPC Biotech, which owned the rights to satraplatin, withdrew its FDA filing for accelerated approval and merged with Agennix in 2009. Agennix went into liquidation in 2013.

In 2020, Dayton Therapeutics, a firm led by a team of experienced oncologists, acquired all satraplatin related rights and data. The firm is now using its innovative AI-powered genetic and molecular research model to investigate new therapeutic uses for this drug candidate based on recent advances in genetics and molecular biology. Satraplatin has shown in lab studies to attack specific blood cancer variants not only via its platinum effect of DNA damage to cancer cells, but also indicating the recovery of the cell death process within cancer cells, and by targeting their mutational vulnerabilities.

Satraplatin would be the first platinum based drug that can be administered orally and over a convenient 5 day schedule. Compared to other platinum drugs like cisplatin and carboplatin, satraplatin has a milder toxicity profile in terms of damage to kidneys and nervous system. Extensive clinical safety data is available regarding the use of satraplatin dating back to 2007.

Commenting on the firm's future plans for satraplatin, Dr Felix Dahm, the CEO of Dayton Therapeutics said, "In 2007, the technology and knowledge base that exists today was not available. Thus, satraplatin's true potential went unexplored and it was shelved before further studies were conducted. We didn't just acquire satraplatin, but are developing it further. Earlier, satraplatin was seen as a broad stroke drug against solid tumors. We just used the latest developments in the field of AI, molecular biology and genetics to discover new uses for a drug that might have otherwise never been developed. We acquired all the data and rights associated with satraplatin, and have already filed two patents - one related to the indications and one around the actual molecular targets in the patients. What really matters to us is the impact that the use of satraplatin can make in the treatment of rare lymphomas and to meet multiple unmet clinical needs. We therefore hope to do our bit to mitigate the suffering that cancer causes to individuals, families and to society as a whole."

About Dayton Therapeutics:

Dayton Therapeutics is a clinical oncology company that specializes in the identification of compounds for the treatment of new cancer indications with limited therapeutic options. The company is currently leveraging proprietary oncologist know-how, AI and data mining to develop satraplatin as a precision platinum for the treatment of rare lymphomas.

Media Contact:Name: Felix Dahm, MDEmail: [emailprotected]

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/137169

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Malaria vax promising, to be cheap too – The Hans India

Posted: September 16, 2022 at 2:36 am

A vaccine candidate, called R21, has been shown to be up to 80% effective at preventing malaria in young children, according to the latest trial results. This follows from a study published in 2021 from the same team at Oxford University which showed that the three-dose vaccine was up to 77% effective at preventing malaria. Their latest study shows that a booster, given a year later, maintains the levels of protection at 70% to 80%, suggesting that long-term protection is possible.

The Oxford researchers told the BBC that their vaccine can be made for "a few dollars," and they have a deal to manufacture over 100 million doses a year. However, there is still a large hurdle to overcome. Phase 3 clinical trials the final phase of testing in humans before regulatory approval can be sought are yet to be conducted.

Crucially, say the scientists, their vaccine is cheap and they already have a deal to manufacture more than 100 million doses a year.

The charity Malaria No More said recent progress meant children dying from malaria could end "in our lifetimes." It has taken more than a century to develop effective vaccines as the malaria parasite, which is spread by mosquitoes, is spectacularly complex and elusive. It is a constantly moving target, shifting forms inside the body, which make it hard to immunise against. Last year, the World Health Organization gave the historic go-ahead for the first vaccine - developed by pharmaceutical giant GSK - to be used in Africa. However, the Oxford team claim their approach is more effective and can be manufactured on a far greater scale. Trial results from 409 children in Nanoro, Burkina Faso, have been published in the Lancet Infectious Diseases. It shows three initial doses followed by a booster a year later gives up to 80% protection, according to the BBC.

A long road with many dead ends

The quest to develop a malaria vaccine began almost 100 years ago. As early as the 1940s, attempts to protect against malaria infection by injecting inactivated parasites were conducted in animals and in humans. Since then, relentless efforts continued until advances in biochemistry and molecular biology made it possible for scientists to isolate proteins from the plasmodium parasite that causes malaria to use in the vaccine and make them in a lab. These proteins were predicted to induce better immunity against infection.

Although the parasite has the same proteins, their accessibility and exposure to the immune system can be less effective at inducing a response. Also, using inactivated whole parasites bring other potential problems, such as toxicity and even the re-activation of the parasite causing an active infection. These modern techniques led to the development in the late 1980s of the SPf66 vaccine that comprised several synthetic molecules of the parasite that were known to be recognised by the immune system in humans.

The vaccine, which was developed in Colombia, was trialled in various countries in South America, achieving an efficacy of 35% to 60%. But when testing was extended to other continents, efficacy was lower: 8% to 30% in Africa and no protection at all in Asia.

Though disappointing, these findings were encouraging because some immunity was achieved, showing that a vaccine against the biggest killer in the tropical world is possible. Many vaccines were designed since using different components of the parasite and tested in clinical trials, including RTS,S which became the first licensed anti-malaria vaccine. It contains part of a major protein found on the surface of the parasite that starts the infection: the so-called sporozoite stage that infects the liver. RTS,S was widely tested in Africa, reaching levels of protection of around 40% that decreased with time. It is based on the same parasite molecule used in R21.

Achieving high levels of protection against malaria has proven very difficult. Even in those cases when promising results were obtained, the effectiveness decreased dramatically when testing the vaccines more widely. Another issue is that, very often, immunity gained from these candidate vaccines fell over time. Long-term immunity is important because the risk of infection continues throughout life, particularly in areas where transmission is high.

Why it's been so hard

Advances in gene sequencing in the past few decades have allowed us to analyse the malaria-causing parasite's genome. The sequencing of samples from patients from around the world changed our understanding of the parasite and the disease. It became clear that there isn't one parasite but many genetically distinct strains. And this diversity is reflected in the components of the parasite, including those used in the vaccines.

Because the vaccines were developed with strains of parasites kept in laboratories, the identity of the vaccine is restricted to that particular parasite and, as a result, the immune system will be trained to recognise similar parasites but not necessarily other genetically different strains. This problem is increased by the complexity of the life cycle of these parasites and the differences in the dynamics of the infection in different regions of the world. In Africa, the transmission of the disease is high and, as a result, it is common that people get infected with several genetically different parasites. So if the vaccine is effective against limited genetic versions, then some will be eliminated by the immune system but not others. This is a major problem in developing an effective vaccine against malaria because it makes it difficult to eliminate the parasite from the body. This might also be at least part of the reason most vaccines tested so far have low protection which wanes over time.

The high level of protection obtained with R21, the malaria vaccine developed by scientists at Oxford University, is really promising. The protection it gives will be followed closely with great expectations to find out whether it can be sustained in the long term.

It will also be very important to test it in different parts of the world to find out if it gives wide protection. And, finally, it will also be helpful to know whether it can protect older children and adults and become a general preventive tool against malaria.

(Writer is a Senior Lecturer, Molecular Genetics, University of Hertfordshire; The Conversation)

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JNCASRs novel molecule prevents obesity in mice – The Hindu

Posted: September 16, 2022 at 2:36 am

Currently, there are no reliable drugs available for obesity and its associated disorders

In spite of all the discipline of diet and exercise, are you still finding it difficult to stay in shape? The developed world suffers from numerous cases of obesity due to a more sedentary mode of life offered by the comforts of the first world. In contrast, in the developing world, due to irregular food habits and economic stress, a large number of individuals have an accumulation of visceral fat especially in the stomach area as well as in the liver.

Although obesity is more of a lifestyle-related health disorder, it can lead to several other diseases such as non-alcoholic fatty liver disease, diabetes and osteoarthritis. Surprisingly, there are no reliable drugs available for obesity and its associated disorders.

While there are several drugs undergoing clinical trials for tackling obesity, many have already fallen through due to undesirable side effects in human patients.

Over the past two decades, our laboratory has been working on how the modifications of the gene rather than the gene sequence itself can regulate gene function. This branch of molecular biology is called epigenetics. The epigenetic changes are reversible and directly correlated with habits as well as social and environmental cues.

Our genetic material DNA is wrapped around protein balls called histones to form the highly organised genome. Different chemical modifications of both DNA and histones can dictate the fate of genes in terms of them being switched on or remaining switched off. This on/off balance of gene expression is critical for health and disease.

We have discovered that one such rarely studied chemical modification of histone lysine butyrylation is critical for fat cell development that underlies obesity manifestation. This finding encouraged us to search for a small molecule that could specifically inhibit this modification and thereby arrest or ameliorate obesity.

After many years of effort, we could finally demonstrate that a semi-synthetic derivative of garcinol, a molecule naturally found in Garcinia indica (kokum) fruit rind, could selectively reduce the levels of this modification by inhibiting the catalytic activity of the enzyme responsible for it the master epigenetic enzyme p300.

Since this molecule (LTK-14A) is very specific for only one enzymatic activity of the multi-functional enzyme p300, we expected minimal toxicity from this compound for biological applications.

As per traditional knowledge, kokum ( Garcinia indica) extracts have been known to have a protective effect against obesity. However, its exact molecular targets were not known. Furthermore, its major chemical constituent garcinol was found to be toxic as it targets many enzymes non-specifically.

Our semi-synthetic molecule, LTK-14A, could offer greater efficacy due to targeted inhibition of the less abundant butyrylation modification that becomes relevant in the context of fat cell development.

We have found that this molecule not only inhibits fat synthesis in mice cell line but also prevents obesity in mice feeding on high fat-diet. Very significantly, this molecule could reduce the weight of genetically obese and highly diabetic mice as well. Furthermore, administration of this inhibitor could reduce fat accumulation in the liver also, making it a suitable candidate for being used against non-alcoholic fatty liver disease.

We have also performed a few pre-clinical tests which indicate that this molecule is almost non-toxic. To increase its efficacy, we have also made a formulation with this molecule as its active component.

This discovery is all set for the next stages of drug development.

Our work on the discovery of this novel regulatory mechanism of obesity manifestation and its specific inhibitor has recently been accepted for publication in the Journal of Medicinal Chemistry.

This entire work is a result of a collaboration between scientists from the Transcription and Disease Laboratory, Molecular Biology and Genetics Unit of Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru and CSIR-Central Drug Research Institute, Lucknow.

( Tapas K. Kundu and Aditya Bhattacharya are from the Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru.)

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Adva Biotechnology is using artificial intelligence to manufacture cell therapies – Labiotech.eu

Posted: September 16, 2022 at 2:35 am

The manufacturing of cell therapies is highly complex, often depending on skilled manual labor. The Israeli startup Adva Biotechnology aims to use automation, optical sensing and artificial intelligence to remove the manual component from the process.

Cancer cell therapies such as CAR-T immunotherapies have demonstrated enormous potential for treating forms of blood cancer. Currently available therapies involve extracting a cancer patients immune T cells, genetically engineering them in the lab, and returning them to the patient to kill cancer cells.

One of the drawbacks of these therapies is that growing cells in a manufacturing setting is highly complex. This means that the therapies are expensive and largely limited to the wealthiest nations.

According to Noam Bercovich, vice president of development at the Israeli firm Adva Biotechnology, CAR-T cell therapies have been something that most cancer patients are unable to receive.

All the companies manufacturing this therapy use semi-automated solutions, which demand lots of human input in terms of quantity and expertise, Bercovich added.

To bring more automation into the cell therapy manufacturing process, Adva Biotechnology was founded in 2016 by its CEO Ohad Karnieli in Bar-Lev High-Tech Park in Israel. Adva Biotechnology is working on an automated cell culture kit powered by artificial intelligence and optical sensors.

Prior to founding Adva Biotechnology, Karnieli had served as vice president of technology and manufacturing at the cell therapy firm Pluristem Therapeutics, which is now known as Pluri. He also founded the CDMO Atvio Biotechnology, which was acquired by Orgenesis in 2018.

Bercovich was a process engineering manager at Pluristem and had known Karnieli for almost 12 years before ADVA Biotechnology was founded.

We worked together and [Karnieli] left the place, called me and told me about his idea. And I said Id join right away, recalled Bercovich.

In an online presentation, Advas founder and CEO Ohad Karnieli explained that current manufacturers are only able to measure a few parameters in cell cultures on a few occasions.

We dont really know whats happening inside the system or inside our cultures, he stated. We put the cells in the incubator and we have no idea whats happening. We need much more in-process controls.

The equipment, named ADVA X, uses sensors and artificial intelligence to handle the fine adjustments that are often required when growing cells, such as monitoring and tweaking levels of nutrients in the cell culture medium. It consists of a single-use kit that slots into an electronic system. According to Adva Biotechnology, the kit can culture from 10 million to 20 billion cells in the same chamber. In addition, the kit has the ability to grow CAR-T cells, natural killer (NK) cells, exosomes, viruses and more.

At present, ADVA X is available only to early adopters. After a patent dispute with the CDMO giant Lonza, Adva entered a licensing agreement with Lonza in May 2022 to enable the startup to launch its equipment in the U.S. The device will face its first field test manufacturing an advanced therapy for a clinical trial in 2023.

Once its tested in a clinical trial that is when we can look at the device and say, We made it. Its the real thing, said Bercovich.

Adva is part of a wave of startups geared towards bringing automation to the world of advanced therapy manufacturing, such as Ori Biotech and Cytera Cellworks. Bercovich said that Advas fast adoption of optical sensing technology is what helps the company stand out from the crowd.

Automated cell therapy manufacturing technology such as the ADVA X could also enable the advent of decentralized manufacturing. In this scenario, for example, a CAR-T therapy could be produced at the hospital where a cancer patient is staying, rather than being shipped off to a large, expensive central location.

If I can take my manufacturing and bring it to the patient, a lot of the logistics and the huge footprint are basically eliminated, stated Karnieli. We need decentralized manufacturing with centralized control, meaning remote access, alerts and all these different automation properties.

Adva Biotechnology bankrolled its research with a crowdfunding campaign in 2020, and with a seed round in 2021. The company is now in the middle of raising another funding round.

According to Bercovich, while a lot of attention has been paid to the business potential of automation in cell therapy manufacture, Advas also mindful that these advances can lead to more treatments that save lives.

Behind all this, its a potential cancer treatment, said Bercovich. This is something that we speak about every now and then to not forget.

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CAR T-Cell Therapy operations launched in Saudi Arabia – Omnia Health Insights

Posted: September 16, 2022 at 2:35 am

CAR T-cell therapy products will soon be available in Saudi Arabia, Singapore and Brazil, following the launch of Gilead and Kite Oncologys latest operations.

Commenting on the expansion into KSA, Eslam Khedr, Regional Business Unit Director for Cell Therapy and Oncology, Gilead and Kite Middle East said: Saudi Arabias Vision 2030 is a key reason Kite selected Saudi Arabia as the location of its first Middle East operation. We are establishing a fully functional oncology/cell therapy business unit in line with international best-in-class protocols with the aim of giving those with cancer the chance to be treated and to offer healthcare of an international standard.

Dedicated Gilead and Kite teams will work to qualify leading hospitals to administer CAR T-cell therapy in each of the new countries after local regulatory approvals. Plans are also in place to increase its workforce in these countries this year.

To date, Kite is the only company dedicated exclusively to the research, development, and manufacturing of cell therapy on a global scale. All its functions dedicated to this focus area are vertically integrated under one leadership team for efficient delivery of the highly specialised and complex end-to-end processes needed to support CAR T-cell therapy.

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Biocytogen Announces Collaboration with FineImmune to Develop TCR-Mimic Antibody-Based Cell Therapy – Business Wire

Posted: September 16, 2022 at 2:35 am

BEIJING & GUANGZHOU, China--(BUSINESS WIRE)--Biocytogen Pharmaceuticals (Beijing) Co., Ltd. ("Biocytogen", HKEX: 02315) announced a strategic collaboration with Guangzhou FineImmune Biotechnology Co., LTD. (FineImmune) to co-develop cell-based therapeutic drugs targeting intracellular tumor-associated antigens. Biocytogen will use its proprietary TCR-mimic antibody platform to discover fully human antibody sequences that will be further developed using FineImmunes unique cell therapy platform.

Biocytogens TCR-mimic antibody development platform utilizes its proprietary fully human antibody RenMiceTM (RenMabTM and RenLite mice) that have been further engineered to express a human leukocyte antigen (HLA) gene. Antibodies against intracellular tumor-associated antigens are subjected to advanced high-throughput antibody screening technologies to discover antibodies with high specificity and affinity.

Most tumor antigens are intracellular, and our TCR-mimic platform provides a solution for developing antibodies against these valuable targets, said Dr. Yuelei Shen, Founder, Chairman and CEO of Biocytogen. TCR-mimic antibodies generated by our TCR-mimic platform have potentials to be developed into multiple drug modalities such as T cell engagers, bispecific/multispecific antibodies and CAR-T therapies. We are pleased to collaborate with FineImmune to explore the application of our antibodies in the field of cell therapies.

FineImmune is a pioneering T cell therapy company, and has solved multiple critical barriers in the microenvironment of solid tumors by using multiple proprietary technology platforms, such as GSOP for T-cell engineering, HAP for TCR identification, CMP for personalized TCR-T cell production and in vivo T-cell delivery platform (TDP). FineImmunes product pipelines include TCR-T, CAR-T, TAL, TIL, etc. The company developed the first personalized neoantigen-specific TCR-T cell therapy, which is in phase I clinical trial now. In addition, FineImmune possesses technologies for the precision prediction of the efficacy and side effects of immunotherapy, enabling healthcare professionals to provide effective and safe immunotherapy to patients with common malignant tumors.

T cells play an important role in treating cancers. Biocytogens advanced TCR-mimic platform makes it possible for us to develop T cell therapies against crucial but low-expressed intracellular tumor antigens, said Dr. Penghui Zhou, Founder and Chief Technology Officer of FineImmune. We focus on providing efficient and safe immunotherapy using advanced technologies. This collaboration will promote the development of new cell therapeutic drugs and the expansion of the potential of immunotherapy to benefit patients.

About the TCR-Mimic Platform Biocytogens T Cell Receptor (TCR)-Mimic platform utilizes HLA-expressing fully human antibody mice (HLA/RenMice) to generate antibodies to intracellular tumor-associated antigens when immunized with MHC-antigen-peptide complexes. Subsequently, Biocytogens high-throughput antibody screening platform aims to swiftly identify TCR-mimic antibodies with higher specificity and affinity than endogenous TCRs derived from patients. Currently, antibody sequences against multiple intracellular targets have been obtained, and their efficacies have been verified in vitro and in vivo. Fully human antibody sequences obtained from the TCR-mimic platform can empower the development of T cell engagers, bispecific/multispecific antibodies, and CAR-T therapies.

About BiocytogenBiocytogen Pharmaceuticals (Beijing) Co., Ltd. is a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies. Using its proprietary RenMabTM /RenLite mice platforms for fully human monoclonal and bispecific antibody development, Biocytogen has integrated its in vivo drug efficacy screening platforms and strong clinical development expertise to streamline the entire drug development process. Biocytogen is undertaking a large-scale project to develop antibody drugs for more than 1000 targets, known as Project Integrum, and has entered ongoing collaborations with dozens of partners worldwide to produce a variety of first-in-class and/or best-in-class antibody drugs. The company's pipeline includes 12 core products, among which two products are in phase II multi-regional clinical trials and two products are in phase I. Headquartered in Beijing, Biocytogen has branches in Haimen Jiangsu, Shanghai, Boston, USA and Heidelberg, Germany. On September 1, 2022, Biocytogen was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 02315.HK. For more information, please visit http://en.biocytogen.com.cn.

About FineImmuneGuangzhou FineImmune Biotechnology Co., Ltd. is an innovation driven company based in China. The company is mainly engaged in the development of solid tumor immunotherapy drugs and related businesses. It has solved key technical bottlenecks in solid tumor immunotherapy and possesses core technologies. A number of T-cell therapy products for solid tumors are in clinical trials, as well as diagnostic reagents for accurate identification of effective populations. It has a 2000 square meter immunotherapy R&D laboratory and a GMP production workshop for cell therapy products in Guangzhou Science City. The company's individualized TCR-T cell therapy product (new drug) has been carried out clinical research in the Affiliated Tumor Hospital of Sun Yat sen University. At present, more than 20 immune cell therapy products and technologies are under research and development. For more information, please visit http://www.fineimmu.com/.

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Biocytogen Announces Collaboration with FineImmune to Develop TCR-Mimic Antibody-Based Cell Therapy - Business Wire

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Cell Therapy Technologies Markets, 2027 – Emergence of IPSCs as Alternatives to ESCs & Increased Focus on Personalized Medicine -…

Posted: September 16, 2022 at 2:35 am

DUBLIN--(BUSINESS WIRE)--The "Cell Therapy Technologies Market by Product (Media, Sera & Reagents, Cell Culture Vessels, Single Use Equipment, Systems & Software), Process (Cell Processing), Cell Type (T-cells, Stem Cells), End User (Biopharma, CMOs), Region - Global Forecast to 2027" report has been added to ResearchAndMarkets.com's offering.

The cell therapy technologies market is projected to reach USD 8.0 Billion by 2027 from USD 4.0 Billion in 2022, at a CAGR of 14.6%

The growth can be attributed to the increasing public-private partnerships. Several government and private organizations have made significant investments to strengthen R&D in cell therapy leading to a surge in cell therapy technologies demand, hence propelling market growth.

Cell therapy instruments and consumables are used in the development of novel cell therapies for the treatment of different diseases and the mass production of cells from given samples or tissues.

Cell therapy technologies find major applications in regenerative medicine, stem cell research, cancer research, and cell biology research. These technologies are also extensively used in research centers and research institutes for life science and biopharmaceutical R&D.

The rising government investments in cell-based research, increasing incidence of chronic and infectious diseases, a large number of oncology-related cell therapy clinical trials, and increasing GMP certifications for cell therapy production facilities are the key factors driving the growth of this market.

The cell preservation and distribution and handling process segment accounted for the second largest share of the market in 2021.

Cell preservation and distribution is an essential and vital step in the cell scaling-up process. In addition, with the growth in the demand for cell-based medical products and therapies, the demand for reliable storage equipment to preserve finite cell lines and cells manufactured in excess is expected to increase. This factor is expected to drive the growth of this market segment.

The CROs and CMOs accounted for the second largest share of the cell therapy technologies market in 2021.

To cater the large demand, pharmaceutical companies need to speed up clinical timelines, maintain business continuity, and free up resources for projects. This has increased outsourcing analytical tests to CROs and CMOs, thereby boosting the segment market growth.

Asia Pacific: The fastest-growing region in the cell therapy technologies market.

The Asia Pacific market is expected to register the highest CAGR during the forecast period. Some of the major factors contributing to the growth of the Asia Pacific market are low-cost manufacturing advantage, increasing per capita income, and the growing need to curb cancer. In addition, the growth of the geriatric population is also fueling the cell therapy technologies market in the region.

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For more information about this report visit https://www.researchandmarkets.com/r/2wd9fd

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TIL Therapy as a Personalized Treatment Strategy for NSCLC – Targeted Oncology

Posted: September 16, 2022 at 2:35 am

Advancements in immune checkpoint inhibitors (ICIs) have revolutionized oncology therapy.1 Several ICIs targeting PD-1 or PD-L1 are available for the treatment of advanced nonsmall cell lung cancer (NSCLC).1,2 However, there remains a need for alternative treatments due to ICI resistance, failure to respond to therapy, or disease relapse.2-5 Even when ICIs are used in combination with chemotherapy, patients may experience cancer progression within 12 months.6 Oncology providers should identify opportunities for clinical trials and investigational strategies that provide options for patients with advanced NSCLC beyond ICIs and biomarker-directed therapies.

Adoptive cell therapy (ACT) is a type of immunotherapy where an individuals immune cells are harvested and expanded to help elicit a tumor-specific, cell-mediated response against cancer cells; it includes chimeric antigen receptor (CAR) T-cell therapy (CAR-T), engineered T cell receptor (TCR)-based T cell (TCR-T) immunotherapy and tumor-infiltrating lymphocytes (TILs).7 The first promising results evaluating the use of autologous (self) TILs in patients with metastatic melanoma were published in 1988, and they sparked further research.7,8

Endogenous TILs

Endogenous TILs are composed of T cells isolated from tumor tissue that can recognize tumor-specific antigens to target and attack cancer cells.9,10 In most cancers, immune infiltrate includes various macrophage subtypes and several different types of T lymphocytes.11 Helper T lymphocytes and cytotoxic T lymphocytes (CTLs) play an important role in identifying cancer cells and arresting their growth.

During tumorigenesis, genetic instability can lead to somatic mutations producing new proteins, or neoantigens, in cancer cells. Neoantigens expressed only in tumor cells are referred to as tumor-specific antigens (TSAs). All T cells, including CTLs, express a unique T-cell receptor (TCR) specific to a single TSA. Major histocompatibility complex molecules present TSAs on the tumor cell surface, which are recognized upon TCR binding. Once tumor cells are recognized as non-self, T-cell activation occurs.12,13 CTLs release cytotoxic granules, which fuse with the target cell membrane. Granulysin and perforin create pores in the cell membrane, allowing granzymes to be released into the cytoplasm. Granzymes then initiate a caspase cascade leading to apoptosis.1,14,15 However, tumor cells can initiate adaptive mechanisms to evade CTL activity, including the production of immunosuppressive cytokines that can impede the antitumor immune response.9,16 Therefore, methods to overcome immune evasion and improve upon TIL-mediated tumor cell destruction have been explored.

Development and Potential Utility of TILs for Treatment of Solid Tumors

As noted above, endogenous TILs possess TCRs with the ability to recognize and destroy tumor cells. Removing TILs from the immunosuppressive tumor environment through tumor excision allows for ex vivo assessment of antitumor activity. Once highly active TILs are identified, they are rapidly expanded to produce billions of activated, tumor-specific T cells, which are then infused back to the host to target and destroy tumor cells (Figure).13 This approach has potential utility for treating a variety of solid tumors, including NSCLC.7,17-19

Addressing Limitations of Current Treatment Strategies

TIL Therapy in Immunologically Cold Tumors

NSCLC tumors are often categorized as immunologically cold, meaning that they have features thought to impede a strong immune response, including the lack of TILs within the tumor microenvironment. This may be due to a lack of tumor antigens, defective recruitment of antigen-presenting cells, lack of T-cell costimulation and activation, and modified production of chemokines and cytokines involved in cell trafficking and activation.6,20 TIL therapy may improve immunological response within the tumor by providing more T cells to mount an attack. Moreover, TIL therapy given in combination with an ICI may help to prevent T-cell inactivation via tumor-mediated mechanisms once they have infiltrated the tumor.4,21

Limitations With Other Adoptive Cell Therapies

ACT methodologies are centered around the manipulation of an individuals own immune cells to generate a tumor-specific, cell-mediated response against cancer.7 However, CAR-T and TCR-T therapies have faced challenges in the treatment of solid tumors, including the lack of stable tumor antigen expression and the need for human leukocyte antigen restriction. Severe and unpredictable toxicities can also occur with CAR-T and TCR-T due to cross-reactivity or trace expression of tumor-associated antigens in healthy cells.22-24 Further, acquired resistance can occur following a clinical response, which may be attributed to deletion or mutation of the target antigen, antigenic heterogeneity, or impaired trafficking.6,24,25

Unlike other ACTs, TILs are composed of polyclonal cells capable of simultaneously recognizing multiple tumor antigens.19 TILs are derived from genetically unmodified host cells, which may reduce the risk for complications from immune-mediated responses. TILs are also capable of targeting truncal neoantigens clonally expressed by a cancer cell, which may reduce the risk of resistance due to deficient target antigen expression.7

Durable Remissions With TIL Therapy

TIL therapy has the potential for durable, complete remissions.26 This partially is due to the transdifferentiation potential and lifespan of memory T cells.6 Such responses have been observed in heavily pretreated patients with metastatic melanoma after disease progression following treatment with chemotherapy, IL-2, antiCTLA-4 monoclonal antibodies, or a combination of these.26 Additionally, durable remissions following TIL therapy have been reported in a variety of other solid tumor types, including cholangiocarcinoma and cervical, colorectal, and breast cancers.27-30

Future Directions

Clinical trials in metastatic melanoma have demonstrated complete and durable responses from TIL therapy, even in patients who progressed on multiple prior therapies, including antiPD-1 agents.31,32 These findings suggest that TIL therapy may be a viable option for patients with PD-1 resistance or in cancers with lower immunogenicity. Observed similarities between NSCLC and melanoma suggest a role for TIL therapy in the treatment of NSCLC and warrant further investigation.

For information regarding advancements in TIL therapy, resources and further information are available from TILs Working Group at https://www.tilsinbreastcancer.org/.

References

1. Raskov H, Orhan A, Christensen JP, Gogenur I. Cytotoxic CD8+ T cells in cancer and cancer immunotherapy. Br J Cancer. 2020;124:359-367. doi:10.1038/s41416-020-01048-4

2. Horvath L, Thienpont B, Zhao L, Wolf D, Pircher A. Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook.Mol Cancer. 2020;19(1):141. doi:10.1186/s12943-020-01260-z

3. Nowicki TS, Hu-Lieskovan S, Ribas A. Mechanisms of resistance to PD-1 and PD-L1 blockade.Cancer J. 2018;24(1):47-53. doi:10.1097/PPO.0000000000000303

4. Adoptive cell therapy plus checkpoint inhibitors show promise in non-small cell lung cancer. New release. Moffitt Cancer Center. August 12, 2021. Accessed July 29, 2022. https://moffitt.org/newsroom/press-release-archive/adoptive-cell-therapy-plus-checkpoint-inhibitors-show-promise-in-non-small-cell-lung-cancer/

5. Pathak R, Pharaon RR, Mohanty A, Villaflor VM, Salgia R, Massarelli E. Acquired resistance to PD-1/PD-L1 blockade in lung cancer: mechanisms and patterns of failure.Cancers (Basel). 2020;12(12):3851. doi:10.3390/cancers12123851

6. Creelan BC, Wang C, Teer JK, et al. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial.Nat Med. 2021;27(8):1410-1418. doi:10.1038/s41591-021-01462-y

7. Hulen TM, Chamberlain CA, Svane IM, Met O. ACT up TIL now: the evolution of tumor-infiltrating lymphocytes in adoptive cell therapy for the treatment of solid tumors. Immuno. 2022;1(3):194-211. doi:10.3390/immuno1030012

8. Rosenberg SA, Packard BS, Aebersold PM, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report.N Engl J Med. 1988;319(25):1676-1680. doi:10.1056/NEJM198812223192527

9. Zur RT, Adler G, Shamalov K, et al. Adoptive T-cell immunotherapy: perfecting self-defenses. In: Klink M, Szulc-Kielbik I, eds. Interaction of Immune and Cancer Cells. Springer International Publishing AG; 2022:253-294.

10. Investigational TIL Therapy. Iovance Biotherapeutics. 2022. Accessed September 8, 2022. https://www.iovance.com/about-til/

11. Linette GP, Carreno BM. Tumor-infiltrating lymphocytes in the checkpoint inhibitor era.Curr Hematol Malig Rep. 2019;14(4):286-291. doi:10.1007/s11899-019-00523-x

12. Zhang Z, Lu M, Qin Y, et al. Neoantigen: a new breakthrough in tumor immunotherapy.Front Immunol. 2021;12:672356. doi:10.3389/fimmu.2021.672356

13. Qin SS, Melucci AD, Chacon AC, Prieto PA. Adoptive T cell therapy for solid tumors: pathway to personalized standard of care.Cells. 2021;10(4):808. doi:10.3390/cells10040808

14. Cullen SP, Brunet M, Martin SJ. Granzymes in cancer and immunity.Cell Death Differ. 2010;17(4):616-623. doi:10.1038/cdd.2009.206

15. Nirmala JG, Lopus M. Cell death mechanisms in eukaryotes.Cell Biol Toxicol. 2020;36(2):145-164. doi:10.1007/s10565-019-09496-2

16. Vinay DS, Ryan EP, Pawelec G, et al. Immune evasion in cancer: mechanistic basis and therapeutic strategies.Semin Cancer Biol. 2015;35(suppl):S185-S198. doi:10.1016/j.semcancer.2015.03.004

17. Sarnaik AA, Hamid O, Khushalani NI, et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J Clin Oncol. 2021;39(24):2656-2666. doi:10.1200/JCO.21.00612

18. Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response.Nat Rev Immunol. 2012;12(4):269-281. doi:10.1038/nri3191

19. Wang S, Sun J, Chen K, Ma P, et al. Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors.BMC Med. 2021;19(1):140. doi:10.1186/s12916-021-02006-4

20. Bonaventura P, Shekarian T, Alcazer V, et al. Cold tumors: a therapeutic challenge for immunotherapy.Front Immunol. 2019;10:168. doi:10.3389/fimmu.2019.00168

21. Lanitis E, Dangaj D, Irving M, Coukos G. Mechanisms regulating T-cell infiltration and activity in solid tumors.Ann Oncol. 2017;28(suppl 12):xii18-xii32. doi:10.1093/annonc/mdx238

22. Blumenschein GR, Devarakonda S, Johnson M, et al. Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+advanced non-small cell lung cancer.J Immunother Cancer. 2022;10(1):e003581. doi:10.1136/jitc-2021-003581

23. Duinkerken CW, Rohaan MW, de Weger VA, et al. Sensorineural hearing loss after adoptive cell immunotherapy for melanoma using MART-1 specific T cells: a case report and its pathophysiology.Otol Neurotol. 2019;40(7):e674-e678. doi:10.1097/MAO.0000000000002332

24. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies.Blood Cancer J. 2021;11(4):69. doi:10.1038/s41408-021-00459-7

25. Haas AR, Tanyi JL, O'Hara MH, et al. Phase I study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers.Mol Ther. 2019;27(11):1919-1929. doi:10.1016/j.ymthe.2019.07.015

26. Rosenberg SA, Yang JC, Sherry RM, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy.Clin Cancer Res. 2011;17(13):4550-4557. doi:10.1158/1078-0432.CCR-11-0116

27. Zacharakis N, Chinnasamy H, Black M, et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer.Nat Med. 2018;24(6):724-730. doi:10.1038/s41591-018-0040-8

28. Stevanovi S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells.J Clin Oncol. 2015;33(14):1543-1550. doi:10.1200/JCO.2014.58.9093

29. Tran E, Robbins PF, Lu YC, et al. T-cell transfer therapy targeting mutant KRAS in cancer.N Engl J Med. 2016;375(23):2255-2262. doi:10.1056/NEJMoa1609279

30. Tran E, Turcotte S, Gros A, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer.Science. 2014;344(6184):641-645. doi:10.1126/science.1251102

31. Robertson J, Salm M, Dangl M. Adoptive cell therapy with tumour-infiltrating lymphocytes: the emerging importance of clonal neoantigen targets for next-generation products in non-small cell lung cancer.Immunooncol Technol. 2019;3:1-7. doi:10.1016/j.iotech.2019.09.003

32. Dafni U, Michielin O, Lluesma SM, et al. Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis.Ann Oncol. 2019;30(12):1902-1913. doi:10.1093/annonc/mdz398

Figure. Development Process of TIL Therapy for Solid Tumors13

TIL, tumor-infiltrating lymphocyte.

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TIL Therapy as a Personalized Treatment Strategy for NSCLC - Targeted Oncology

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Cell Therapy Technologies Markets, 2027 – Emergence of IPSCs as Alternatives to ESCs & Increased Focus on Personalized Medicine -…

TIL Therapy as a Personalized Treatment Strategy for NSCLC – Targeted Oncology

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