SITC 2022 | Tmod cellular logic gate as a solution to on-target, off-tumor toxicity in CAR-T for solid tumors

J. Randolph Hecht, MD, University of California, Los Angeles, CA, discusses Tmod CAR-T cell therapy, an autologous logic-gated cell therapy with an interchangeable activator and inhibitory receptor gated by HLA-A*02 to target colorectal, pancreatic, and lung cancer. At the Society for Immunotherapy in Cancer (SITC 2022), data was presented on Tmod’s with activators targeting CEA, which is found in multiple epithelial tumors including pancreatic, lung and colorectal cancer, and mesothelin, which is expressed in various tumors including pancreatic cancer. CEA and mesothelin are also expressed in normal tissue, which has previously contributed to significant on-target, off-tumor toxicity in cellular therapies. However, the Tmod additionally consists of a blocker that recognizes a second surface antigen from an allele lost only in tumor cells, HLA loss of heterozygosity (LOH), occurring in approximately 20% of major malignancies including lung, pancreatic and colorectal cancer, to combat the major challenge of on-target, off-tumor toxicity. The ongoing BASECAMP-1 (NCT04981119) trial is determining and identifying patients with somatic HLA LOH eligible for Tmod CAR T-cell therapy and manufacturing feasibility for future Tmod CAR T-cell trials. This interview took place at the 37th Annual Meeting of the Society for Immunotherapy in Cancer (SITC 2022) in Boston, MA.

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