On July 27, 2023 Cellinfinity Bio, a privately held biotechnology company developing first/best-in-class cell therapy products against solid tumors and other diseases, reported the publication of a novel CAR enhancement, the addition of CTLA-4 intracellular domain to improve anti-tumor CAR-T activity (Press release, Cellinfinity Bio, JUL 27, 2023, View Source [SID1234633472]). This technology is published in Nature Immunology on July 27. Trogocytosis is a process where cancer antigens are transferred onto immune cells, including T-cells; if the cancer antigen is a target of CAR-Ts, this results in CAR-Ts killing each other or fratricide. The addition of intracellular domain of CTLA-4 prevented trogocytosis and resulted in improved CAR-T survival, including maintenance of central memory T-cells and increased T-cell persistence – all leading to stronger anti-tumor efficacy. Cellinfinity Bio has an exclusive license of the published CTLA-4 tail technology from Yale University and Professor Sidi Chen’s lab, Founder of Cellinfinity Bio and Associate Professor of Genetics, Yale University.
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"Trogocytosis and fratricide substantially limit current CAR-T cell therapy response. We found a portion of CTLA-4 intracellular domain when fused onto CAR sequence optimizes CAR-T function and results in low trogocytosis, greater durability, and more potent in vitro and in vivo anti-tumor efficacy," said Sidi Chen. "Furthermore, the simple addition of CTLA-4 tail onto CARs has potential to improve CAR-Ts against diverse targets."
"Cellinfinity has identified several important gene enhancements and CAR modifications that improve anti-tumor activity of adoptive cell therapy," added Premal Patel, M.D., Ph.D., Chief Executive Officer, Cellinfinity Bio. "We intend to evaluate this CTLA-4 tail technology across diverse next generation of CAR-Ts targeting variety of cancers." Cellinfinity holds exclusive rights to the CTLA-4 tail technology, as well as exclusive license to other novel cell evolution technologies from the Chen lab at Yale University, that allow whole-genome gain-of-function and loss-of-function genetic screens.