A possible way to reenergize T cells exhausted from fighting a tumor

Medical Xpress | January 28, 2019

An international team of researchers has found a possible way to reenergize T cells exhausted from fighting a cancerous tumor. In their paper published in the journal Science Immunology, the group describes their study of the impact of a decrease in enolase 1 on T cells and how bypassing it allowed them to recharge immune cells. Prior research has shown that one of the reasons the immune system is sometimes unable to fight off a cancerous tumor is because tumor-infiltrating lymphocytes (TILs) lose energy as they attack a tumor. The tired T cells become incapable of putting up a strong fight and the tumor grows bigger. Prior research has also suggested that the reason such cells become tired is that they are outcompeted for glucose by hungry tumor cells. In this new effort, the researchers sought to find a way to overcome this problem so that TILs could continue to fight.
The researchers began by studying T cells, (CD8+ TILs) both in their dormant state and when active. They found that the cells did become exhausted after battling cancer cells for a time. More specifically, they found that T cell exhaustion was caused by a lowered amount of enolase 1, an enzyme found in the glucose metabolic pathway, due to consumption by tumor cells. The end result was a reduction in glucose metabolism and a 10-fold decrease in oxidative phosphorylation

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Watchmaker Genomics Announces Co-Exclusive License to Disruptive DNA Methylation Technology and Strategic Supply Agreements with Exact Sciences

businesswire | August 31, 2023

Watchmaker Genomics, a supplier of innovative products for molecular analysis, today announced a multi-year, co-exclusive agreement with Exact Sciences Corporation, a leading provider of cancer screening and diagnostic tests, to develop and commercialize the breakthrough DNA methylation analysis technology, TET-assisted pyridine borane sequencing (TAPS). Watchmaker will apply its expertise in engineering DNA-modifying enzymes to further improve the TAPS chemistry, ultimately enabling advanced applications, including cancer screening and minimal residual disease (MRD) testing. Under the licensing agreement, Watchmaker may develop and commercialize the TAPS technology under its own brand. DNA methylation patterns offer dynamic and rich insights into the status of both healthy and diseased tissue. These signatures are stable, relatively abundant, and often measurable in the blood, making them promising biomarkers in minimally invasive liquid biopsies. TAPS has the potential to dramatically improve DNA methylation analysis accuracy by enabling a direct readout of cytosine methylation with less template damage and noise when compared to existing methods.1 "Exact Sciences is a leader in cancer screening, and this agreement is a great fit with Watchmaker’s core competencies in next-generation sequencing and genomics applications," said Brian Kudlow, Ph.D., Chief Scientific Officer at Watchmaker Genomics. "It aligns with our belief that multimodal genomic and epigenomic assays represent the frontier of numerous liquid biopsy applications, including early cancer detection." In addition to the development and licensing agreement, the companies have entered into a long-term strategic supply agreement. Under its terms, Watchmaker will provide Exact Sciences with access to its portfolio of best-in-class sequencing reagents and precision enzymes. These products have the potential to enhance the performance of Exact Sciences’ tests while significantly reducing associated costs. “Our company’s mission is to develop and broadly commercialize tools that improve the efficiency of capturing and interpreting the biological information required for many advanced genetic testing applications,” said Trey Foskett, CEO of Watchmaker Genomics. “This arrangement provides us with an exciting opportunity to accelerate the development and commercialization of a game-changing technology to the benefit of the broader research and clinical genomics markets.” About Watchmaker Genomics Watchmaker Genomics applies advanced enzymology to enable breakthrough applications for the reading, writing, and editing of DNA and RNA. The company combines domain expertise in protein engineering with large-scale enzyme manufacturing to address the demanding quality, performance, and scale requirements of high-growth clinical genomics applications. Watchmaker's product portfolio includes enzymes and kits for next-generation sequencing, synthetic biology, and molecular diagnostics. A leading provider of cancer screening and diagnostic tests, Exact Sciences gives patients and health care professionals the clarity needed to take life-changing action earlier. Building on the success of the Cologuard® and Oncotype® tests, Exact Sciences is investing in its pipeline to develop innovative solutions for use before, during, and after a cancer diagnosis.

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Replimune and Incyte Enter into Clinical Trial Collaboration and Supply Agreement to Evaluate RP1 and INCB99280 in Patients

Businesswire | August 02, 2023

Replimune Group, Inc. a clinical stage biotechnology company pioneering the development of a novel portfolio of tumor-directed oncolytic immunotherapies, and Incyte a global biopharmaceutical company, today announced a clinical trial collaboration and supply agreement to study RP1, Replimune’s lead product candidate, in combination with INCB99280, Incyte’s small molecule oral PD-L1 inhibitor. “We are excited to enter into this collaboration with Incyte to explore the use of RP1 prior to surgery as we believe that our tumor-directed oncolytic immunotherapies could have a great impact in the neoadjuvant setting both in cutaneous squamous cell carcinoma (CSCC) and in other cancer types, given the high rates of complete responses we’ve seen to date, and data indicating RP1 is generally very well tolerated,” said Robert Coffin, Chief Research and Development Officer of Replimune. “The unique potential of the RPx platform to induce a patient-specific anti-tumor immune response with an off-the-shelf treatment speaks to the practicality and broad potential utility of the approach, and exploring its use with Incyte’s oral PD-L1 inhibitor has the potential to improve the patient experience further.” “We look forward to collaborating with Replimune on this study evaluating INCB99280 and RP1 in patients with CSCC. Our oral PD-L1 program has shown promising safety and efficacy in early studies thus far, and we look forward to adding to the growing body of evidence for INCB99280 and learning more about its potential to improve clinical outcomes,” said Lance Leopold, M.D., Group Vice President, Clinical Development Hematology and Oncology, Incyte. Under the terms of the agreement, Incyte will initiate and sponsor the clinical trial of INCB99280 and RP1 in patients with high risk, resectable cutaneous squamous cell carcinoma (CSCC), with the clinical trial expected to initiate in early 2024. Replimune will supply Incyte with RP1 for the study and share equally in the costs of the study. About RP1 RP1 is Replimune’s lead oncolytic immunotherapy product candidate and is based on a proprietary new strain of herpes simplex virus engineered for robust tumor selective replication and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF, intended to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response. About INCB99280 INCB99280 is a potent and selective small molecule oral PD-L1 inhibitor, which has demonstrated promising clinical activity and safety in patients with solid tumors. INCB99280 is being evaluated in multiple Phase 2 studies as monotherapy and in combination with other antitumor agents. About Replimune Replimune Group, Inc.headquartered in Woburn, MA, was founded in 2015 with the mission to transform cancer treatment by pioneering the development of novel tumor-directed oncolytic immunotherapies. Replimune’s proprietary RPx platform is based on a potent HSV-1 backbone with payloads added to maximize immunogenic cell death and the induction of a systemic anti-tumor immune response. The RPx platform has a unique dual local and systemic mechanism of action (MOA) consisting of direct selective virus-mediated killing of the tumor resulting in the release of tumor derived antigens and altering of the tumor microenvironment (TME) to ignite a strong and durable systemic response. This MOA is expected to be synergistic with most established and experimental cancer treatment modalities, and, with an attractive safety profile the RPx platform has the versatility to be developed alone or combined with a variety of other treatment options. About Incyte Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics.

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FOXO Technologies Launches Bioinformatics Services to Revolutionize Epigenetic Data Analysis

Businesswire | July 20, 2023

FOXO Technologies Inc.™ a leader in the field of commercializing epigenetic biomarker technology, announced the launch of its cutting-edge Bioinformatics Services to accelerate breakthroughs in biology, biotechnology, and healthcare, and redefine the growing field of epigenetic research. FOXO’s Bioinformatics Services offers a comprehensive platform of advanced data solutions tailored to meet the specific needs of clients in academia, healthcare, and pharmaceutical research. Through its innovative suite of bioinformatic tools, FOXO will enable its clients to increase the speed and accuracy with which they process, analyze, and interpret data sets, accelerate discoveries, and advance their understanding of complex diseases. “The launch of FOXO’s Bioinformatics Services marks a significant milestone for FOXO Technologies and the field of epigenetic research,” said Tyler Danielson, interim CEO and Chief Technology Officer of FOXO. “Epigenetics plays a key role in gene regulation and the interplay between lifestyle and environmental factors on biological systems. However, harnessing the full potential of epigenetic data has long been hindered by the challenges of data processing, analysis, and interpretation. With the introduction of our Bioinformatics Services, we aim to eliminate these barriers and empower researchers, clinicians, and other organizations to accelerate their research.” Any researcher or research group that seeks to leverage DNA methylation microarrays can benefit from FOXO’s Bioinformatics Services. These services include ingesting and processing raw DNA methylation microarray data, performing sample- and probe-level quality control, and securely delivering publication-ready figures and results. FOXO’s expert team also offers the addition of advanced bioinformatic analyses including epigenome wide association studies (EWAS), and even AI-driven epigenetic biomarker development. These services can be applied to Illumina’s existing human and mouse DNA Methylation arrays, which cover over 935,000 and 285,000 CpG sites respectively. By leveraging state-of-the-art algorithms and world-class experts, the company’s bioinformatics platform can rapidly deliver accurate and high-quality data tailored to the needs of each client. “Epigenetics is a nuanced science. Through years of experience, our team has developed niche expertise in bioinformatics with respect to epigenetics, specifically. Researchers who wish to incorporate epigenetic data into their studies can save valuable time and effort through our services offering,” says Brian Chen, Chief Science Officer. As a leader in the field, FOXO remains committed to advancing epigenetic research and catalyzing breakthroughs in health and longevity. With Bioinformatic Services, FOXO is also opening the door to new research collaborations with industry and academic leaders. About FOXO Technologies Inc. FOXO is at the forefront of commercializing epigenetic biomarker technology. Their mission is to utilize the power of epigenetics and artificial intelligence to generate data-driven insights that promote optimal health and longevity outcomes for individuals and organizations alike.

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