On December 10, 2023 Chroma Medicine, Inc., (Chroma) a genomic medicine company pioneering single-dose epigenetic editing therapeutics, reported data demonstrating the potential of its multiplex epigenetic editing platform to enhance functional allogeneic chimeric antigen receptor (CAR) T cells at the American Society of Hematology (ASH) (Free ASH Whitepaper) 65th Annual Meeting in San Diego (Press release, Chroma Medicine, DEC 10, 2023, View Source [SID1234638390]).
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Allogeneic CAR T cell products offer advantages over autologous CAR T cells and have the potential to broaden access to cancer immunotherapy; however, their clinical effect remains limited by lack of durable response and challenges related to immunogenicity and graft-versus-host disease. Incorporating additional edits may help produce cells resistant to rejection—potentially improving allogeneic T cell persistence—but using editing technologies that rely on double- or single-stranded DNA breaks can result in unintended genomic changes. Chroma’s epigenetic editing technology has the potential to provide durable modulation of gene expression without cutting or nicking the DNA, making it well-suited for simultaneous targeting of multiple genes to enhance generation of persistent allogeneic CAR T cells.
"The data presented at ASH (Free ASH Whitepaper) illustrate the tremendous potential of epigenetic editing to accelerate allogeneic CAR T approaches by enhancing functional allogeneic cells to avoid common genotoxic challenges observed in nuclease-based gene editing and base editing," said Vic Myer, Ph.D., Chroma’s President and CSO. "We believe harnessing nature’s innate mechanism for gene regulation unlocks vast opportunity to efficiently, effectively, and simultaneously silence many target genes, and the data presented underscore the strength of this approach in ex vivo cell therapies."
The poster presentation shows Chroma’s epigenetic editor in primary T cells induces durable silencing of T cell receptor and MHC class I and MHC class II expression, maintained through restimulation. The data also demonstrate that multiplex epigenetic editing of CAR T cells does not interfere with cytotoxic anti-tumor function, further highlighting the potential to create CAR T cell therapies with greater accessibility, durability, and efficacy for patients.
Details for Chroma’s poster presentation at the 2023 ASH (Free ASH Whitepaper) Annual Meeting are as follows:
Title: Durable Multiplex Epigenetic Editing for Generation of Allogeneic CAR T Without Chromosomal Rearrangements
Presenter: Jamie Schafer, Ph.D., Associate Director, Ex Vivo Program Sciences, Chroma Medicine
Session: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Session Date and Time: Sunday, December 10, 2023, 6:00 – 8:00p PT
The poster presentation is available on Chroma’s website.