Scientists design protein that prods cancer-fighting T-cells

Medical Xpress | January 09, 2019

Scientists at UW Medicine's Institute for Protein Design (IPD) in Seattle have created a new protein that mimics the action of a key immune regulatory protein, interleukin 2 (IL-2).  IL-2 is a potent anticancer drug and an effective treatment for autoimmune disease, but its toxic side effects have limited its clinical usefulness. In a paper in the Jan. 10 issue of the journal Nature, the researchers report using computer programs to design a protein that they have shown in animal models to have the same ability to stimulate cancer-fighting T-cells as the naturally occurring IL-2, but without triggering harmful side effects. The achievement opens new approaches to the design of protein-based therapeutics for the treatment of cancer, autoimmune diseases, and other disorders, the researchers said. The new protein has been dubbed Neo-2/15 because, in addition to mimicking the effect of IL-2, the protein can also mimic the effect of another interleukin, IL-15, which is being studied as another possible anticancer immunotherapy.

Spotlight

Raymond McCauley is a scientist, engineer, and entrepreneur working at the forefront of biotechnology. Raymond explores how applying technology to life -- biology, genetics, medicine, agriculture -- is affecting every one of us. He uses storytelling and down-to-earth examples to show how quickly these changes are happening, right now, and where it may head tomorrow.

Spotlight

Raymond McCauley is a scientist, engineer, and entrepreneur working at the forefront of biotechnology. Raymond explores how applying technology to life -- biology, genetics, medicine, agriculture -- is affecting every one of us. He uses storytelling and down-to-earth examples to show how quickly these changes are happening, right now, and where it may head tomorrow.

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INDUSTRIAL IMPACT

Adaptive Biotechnologies Announces New Data Demonstrating ImmunoSEQ® Technology Can Identify T-Cell Receptors Associated with Crohn’s Disease

Adaptive Biotechnologies | February 19, 2022

Adaptive Biotechnologies Corporation a commercial stage biotechnology company that aims to translate the genetics of the adaptive immune system into clinical products to diagnose and treat disease, presented data on T-cell receptor (TCR) sequences associated with Crohn’s disease (CD) during an oral presentation today at the 17th Congress of European Crohn’s and Colitis Organisation (ECCO) being held virtually February 16-19. The study identified and characterized TCR sequences associated with CD utilizing Adaptive’s immunoSEQ® technology, providing fundamental insights into the body’s response to CD at the cellular level. The immunoSEQ assay uses sequencing technology to decipher the complexity of the adaptive immune system. This multi-national study, which was also recently published in The Journal of Crohns and Colitis, utilized immunoSEQ technology to analyze TCRs from blood samples of 1,738 CD cases and 4,970 healthy donors. Intestinal tissue samples from a subset of 380 cases were also analyzed. Through this analysis, 1,121 CD-associated TCRs were identified in patients’ blood and verified in tissue. The identification of disease-specific TCRs is an important first step in identifying a signal and developing an algorithm to inform development of a diagnostic test for CD. “The study identified Crohn’s-specific TCRs in both the blood and tissue of patients with Crohn’s disease, including a large subset that are ’public,’ or shared among patients. These findings suggest that blood-based testing for this often-debilitating disease could be used to diagnose and more effectively manage the disease through the identification of these disease specific T-cell receptors.” Matthieu Allez, MD, PhD, Professor and Head, Department of Gastroenterology, Hospital Saint-Louis, Paris T cells can have a significant impact on inflammation in CD, but until now, disease-associated TCRs have been largely unknown and underleveraged in diagnostics for the disease.1 These findings show that immunoSEQ can successfully identify TCRs for CD in a blood sample, which is reflective of the TCRs in intestinal tissue. The average length of time from onset of symptoms to diagnosis for a CD patient can be 1-2 years in the US but may be much longer in other countries, so the potential to open a new path to identify the disease earlier is significant.2,3 Furthermore, the amount of Crohn’s-related TCRs can provide insights into disease characteristics such as the phenotype and location of the disease, with possible clinical implications. In addition to TCR findings, the analysis also studied the possible association between human leukocyte antigens (HLAs) alleles and CD-associated TCRs, which live on most cells in the body, by leveraging the novel immunoSEQ HLA Classifier. HLA alleles are genetic factors that have been found to contribute to a small portion of risk for CD. In this study, nearly 400 CD-associated TCRs were found to be associated with specific HLA alleles. These TCR associations highlight the importance of studying TCRs in the context of HLA type and potentially point to new risk factors and insights for CD such as the involvement of specific antigens that the immune system may be reacting to in people living with CD. “We’re excited to see these results and their potential to advance the scientific community’s understanding of the immune response to Crohn’s disease. The use of immunoSEQ and characterization of TCRs in the blood have the potential to uncover new knowledge on the development and progression of the disease, with the potential to eventually improve diagnostic options and disease management for people living with Crohn’s,” said Harlan Robins, PhD, Chief Scientific Officer and Co-Founder of Adaptive Biotechnologies. “We look forward to continuing our research and advancing the development of our T-Detect test to include an application in the diagnosis of Crohn’s disease.” CD is a subtype of inflammatory bowel disease, a group of diseases impacting about 6.8 million adults globally.4 Early treatment with effective medications can prevent disease progression towards complications, surgery and disability. However, CD is difficult to diagnose and treat, with more than half of patients initially misdiagnosed. No single blood test currently exists for diagnosis of CD. Instead, patients often undergo a series of tests – often invasive – in order to reach a conclusive diagnosis. Based on the results of this study, Adaptive is further investigating specific TCR signatures that are associated with CD related behavior and disease activity to further the development of T-Detect in this indication. Additional research will also focus on signal optimization and clinical validation to explore commercial utility. About the immunoSEQ® Assay Adaptive’s immunoSEQ Assay helps researchers make discoveries in areas such as oncology, autoimmune disorders, infectious diseases and basic immunology. The immunoSEQ Assay can identify millions of T- and/or B-cell receptors from a single sample in exquisite detail. The immunoSEQ Assay is used to ask and answer translational research questions and discover new prognostic and diagnostic signals in clinical trials. The immunoSEQ Assay provides quantitative, reproducible sequencing results along with access to powerful, easy-to-use analysis tools. The immunoSEQ Assay is for research use only and is not for use in diagnostic procedures. About T Detect™ T-Detect™ is a highly sensitive and specific diagnostic test under development for multiple diseases, translating the natural diagnostic capability of T cells into clinical practice. In 2018, Adaptive and Microsoft partnered to build a map of the immune system called the TCR-Antigen Map. This approach uses immunosequencing, proprietary computational modeling, and machine learning to map T-cell receptor sequences to disease-associated antigens for infectious diseases, autoimmune disorders and cancer. From a simple blood draw, T-Detect will leverage the map to provide an immunostatus for an individual, enabling early disease diagnosis, disease monitoring, and critical insights into immunity. T-Detect COVID is the first clinical test launched from this collaboration and the first commercially available T-cell test designed to detect recent or prior SARS-CoV-2 infections. T-Detect COVID is not FDA-cleared or approved, it has received an EUA from the FDA and is available for prescription use only. About Adaptive Biotechnologies Adaptive Biotechnologies is a commercial-stage biotechnology company focused on harnessing the inherent biology of the adaptive immune system to transform the diagnosis and treatment of disease. We believe the adaptive immune system is nature’s most finely tuned diagnostic and therapeutic for most diseases, but the inability to decode it has prevented the medical community from fully leveraging its capabilities. Our proprietary immune medicine platform reveals and translates the massive genetics of the adaptive immune system with scale, precision and speed to develop products in our Immune Medicine and Minimal Residual Disease (MRD) businesses. We have three commercial products and a robust clinical pipeline to diagnose, monitor and enable the treatment of diseases such as cancer, autoimmune conditions and infectious diseases.

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MEDICAL

Merck Enters into Supply Agreement with U.S. Government to Manufacture and Initial Distribution of Investigational Biological Therapeutic

Merck | December 28, 2020

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today declared it has gone into a agreement with the United States Government to help the turn of events, assembling and introductory dispersion of an investigational biological therapeutic (CD24Fc, to be named MK-7110) upon endorsement or Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA). Merck acquired MK-7110 through the securing of OncoImmune, a privately held, clinical-stage biopharmaceutical organization. “Building upon the promising clinical findings to date for MK-7110, Merck is pleased to be collaborating with the U.S. Government to advance the manufacture and distribution of this candidate for patients with serious COVID-19 disease,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. Under the arrangement, Merck will get up to around $356 million for assembling and supply of roughly 60,000-100,000 dosages of MK-7110 to the U.S. Government through June 30, 2021 to meet the public authority's Operation Warp Speed objectives. This methodology is proposed to assist conveyance of MK-7110 to the American individuals as fast as could be expected under the circumstances, following potential EUA or FDA endorsement. Merck is manufacturing contributing to extend its assembling ability to expand supply of MK-7110.

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MEDTECH

Tavotek Biotherapeutics Announces Completion of Round B Financing with $35 Million

Tavotek | November 19, 2021

Tavotek Biotherapeutics, a fast-growing biotech company, announces it has raised $35M in Round B financing. CS Capital, a leading private equity fund manager in China, led this finance round followed by Fontus Capital. This round of financing will be used to accelerate the Phase 1 clinical development of several antibody drugs to start in early 2022. The upcoming antibody drugs were developed by the company based on its TavoPrecise antibody platform for various immune-related disorders. In addition, the funding will also be used to accelerate the CMC and IND development of multiple other oncology pipelines and the development of the company's multicyclic intracellular peptide (MIP) programs. Tavotek Biotherapeutics, established in early 2019, is committed to using innovation to improve the well-being of patients with unmet medical needs. The company has two R&D centers: one in Lower Gwynedd, Pennsylvania and another in Suzhou, China. The core team members have decades of successful drug development experiences at multinational pharmaceutical firms (Johnson & Johnson, Abbott/Abbvie, GlaxoSmithKline and Eli Lilly) which include many blockbuster drugs with annual sales of more than $1 billion. Tavotek's research platforms are built upon three breakthrough technologies: TavoSelect (an innovative Phage Display Library that generates conformational selective human full-length and single domain antibodies); TavoPrecise (a differentiated engineering platform for next generation tissue-specific biologics); and TavoMIP (a multicyclic peptide platform that makes undruggable targets more accessible). With the new infusion of capital, Tavotek is developing novel biologics targeting oncology and autoimmune diseases for patients. The company plans to bring multiple innovative antibodies into human clinical trials in 2022. About Tavotek Tavotek is a biopharmaceutical company focused on discovering, acquiring, developing, and commercializing medicines for patients suffering from debilitating diseases with significant unmet medical needs. Tavotek has a rich pipeline of product candidates at various stages of development for cancer, autoimmune conditions, and inflammatory diseases.

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