Optimizing CAR T Therapies for Gastric Cancer

“We are developing a technology called CycloCAR to try to address the challenges we are facing using CAR T targeting solid tumors, namely CAR T persistence. It also requires strong preconditioning and a lymphodepletion regimen. With CycloCAR, we arm the CAR T using interleukin-7 CCR 21. Hopefully this improves the T cell persistence, and we have some preclinical data that show in animal models, you may not require lymphodepletion anymore.”

CARSgen is developing a next-generation chimeric antigen receptor (CAR) T-cell therapy, CT041, designed to combat challenges with traditional CAR T-cell therapies, namely cell persistence and lymphodepletion requirements. The company’s new technology, termed CycloCAR, which stands for cytokine and chemokine loaded CAR, is designed for increased T-cell recruitment, survival, and proliferation.

Results from a phase 1 trial (NCT03874897) of CT041 in gastric cancer were presented at the 7th Annual CAR-TCR Summit 2022 and were previously published in Nature Medicine. Overall response rate (ORR) was 48.6% and disease control rate (DCR) was 73.0%. The 6-month duration of response rate was 44.8%. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported.

CGTLive spoke with Hong Ma, senior vice president of clinical development for cancer immunotherapy, CARSgen, to learn more about the advantages of CT041 in treating solid tumors. He discussed data from the phase 1 trial and next steps for the therapy.

REFERENCES

1. Ma H. CLDN18.2-targeted CAR T-cell therapy CT041 in subjects with cancers of the digestive system. Presented at: 7th Annual CAR-TCR Summit 2022, September 19-22, Boston, MA.
2. Qi C, Gong J, Li J, et al. Claudin18.2-specific CAR T cells in gastrointestinal cancers: Phase 1 trial interim results. Nat Med. 28, 1189–1198 (2022). doi.org: 10.1038/s41591-022-01800-8