On May 17, 2022 Obsidian Therapeutics, Inc., a biotechnology company pioneering engineered cell and gene therapies, reported it will present enhancements to its proprietary cytoDRIVE technology during a poster presentation at the 25th ASGCT (Free ASGCT Whitepaper) Annual Meeting (Press release, Obsidian Therapeutics, MAY 17, 2022, View Source [SID1234614774]). The conference is being hosted in Washington, D.C., and virtually, May 16-19, 2022.
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The data to be presented outline next-generation advancements to Obsidian’s proprietary cytoDRiVE platform technology, which provides a way to precisely control the timing and level of protein function using FDA approved small molecules. Armoring cell therapies with potent cytokines such as IL12 is a promising approach to treating solid tumors, but uncontrolled constitutive expression of these payloads has limited their clinical use due to toxicity. The data to be presented demonstrate that Obsidian’s cytoDRiVE platform enables robust and reversible regulation of multiple cytokines such as IL12, IL23, IL2, and IFNα, potentially enabling their safe use in adoptive cell therapy applications.
"These advances in our regulation platform expand the versatility and breadth of potential applications for the cytoDRiVE technology," commented Jan ter Meulen, M.D., Ph.D., Chief Scientific Officer of Obsidian. "We look forward to continuing to leverage our technology to advance our pipeline of potential therapies designed to expand available treatment options and improve outcomes of patients using enhanced cell therapies, such as engineered tumor infiltrating lymphocytes."
Details of the poster presentation are as follows:
Poster Board Number: W-215
Session Title: Cancer – Immunotherapy, Cancer Vaccines III
Location: Hall D, Walter E. Washington Convention Center 801 Mt Vernon Pl NW Washington, D.C.
Date and Time: May 18, 2022, 5:30 p.m. to 6:30 p.m. ET
Title: Armoring T-cells with regulatable, membrane tethered cytokines using improved drug-responsive domain technology (cytoDRiVE)
Presenter: Dr. Dhruv K. Sethi, Director, Lead, Discovery & DRD Technologies, at Obsidian Therapeutics
Abstract Summary: Cytokines such as IL12 and IFNα have shown great promise in pre-clinical studies when expressed from genetically modified T-cells, however broad use is limited by toxicity from systemic exposure of constitutive expression. If concentration and localization of cytokines and other immunomodulators could be effectively regulated, they would strong candidates for armoring cellular therapies, such as chimeric antigen receptor T cells (CAR-T cells) or tumor infiltrating lymphocytes (TILs). Advancements to the cytoDRiVE platform, based on multimerization of DRDs with homologous or heterologous oligomerization domains to increase their degron effect, enable tight regulation with extremely low cell surface abundance in the absence of drug, and robust induction (10-20 fold) in the presence of drug. Design elements such as membrane-tethering to reduce risk of systemic toxicity and engineering of protease sites for controlled shedding enable fit-for-purpose engineering and potential to regulate multiple cytokines. cytoDRiVE provides full control of the abundance of IL12, IL23, IL2, and IFNα in genetically modified T-cells using a small molecule drug as the on/off switch for precise control of cytokine activity.