SHANGHAI, December 28, 2022 — CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, announces that the Company and the State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, have jointly developed a new technology that can significantly increase antitumor activities of T cells. The study was recently published on Molecular Therapy.
▲ Screenshot of the publication. Source: https://www.cell.com/molecular-therapy
Limited T cell persistence restrains chimeric antigen receptor (CAR)-T cell therapy in solid tumors. To improve persistence, T cells have been engineered to secrete proinflammatory cytokines, but other possible methods have been understudied. Runx3 has been considered a master regulator of T cell development, cytotoxic T lymphocyte differentiation, and tissue-resident memory T (Trm)-cell formation. A study using a transgenic mouse model revealed that overexpression of Runx3 promoted T cell persistence in solid tumors.
The research team of CARsgen and Shanghai Cancer Institute generated CAR T cells overexpressing Runx3 (Run-CAR-T cells) and found that Run-CAR-T cells had long-lasting antitumor activities and achieved better tumor control than conventional CAR T cells. It was observed that more Run-CAR-T cells circulated in the peripheral blood and accumulated in tumor tissue, indicating that Runx3 coexpression improved CAR T cell persistence in vivo. Tumor-infiltrating Run-CAR-T cells showed less cell death with enhanced proliferative and effector activities. Consistently, in vitro studies indicated that AICD was also decreased in Run-CAR-T cells via downregulation of tumor necrosis factor (TNF) secretion. Further studies revealed that Runx3 could bind to the TNF promoter and suppress its gene transcription after T cell activation.
In conclusion, Runx3-armored CAR T cells showed increased antitumor activities and could be a new modality for the treatment of solid tumors.
▲ Increased antitumor activities of Runx3-armored CAR-T cells
The study was carried out by the team led by Dr. Zonghai Li, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics. Dr. Li is also a professor at the State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine.
Publication URL: https://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(22)00713-4.pdf#%20
About CARsgen Therapeutics Holdings Limited
CARsgen is a biopharmaceutical company with operations in China and the U.S. and is focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors. The Company has built an integrated cell therapy platform with in-house capabilities that span target discovery, antibody development, clinical trials, and commercial-scale manufacturing. CARsgen has internally developed novel technologies and a product pipeline with global rights to address major challenges of CAR T-cell therapies, such as improving the safety profile, enhancing the efficacy in treating solid tumors, and reducing treatment costs. The Company’s vision is to become a global biopharmaceutical leader that brings innovative and differentiated cell therapies to cancer patients worldwide and makes cancer curable.
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