BTRPTB001L

BTRPTB001L is an investigational AND-gated chimeric antigen receptor (CAR) T-cell therapy developed by Biosyngen for the treatment of solid tumors, specifically evaluated in pancreatic cancer models. The therapy is designed to overcome the challenges of on-target, off-tumor (OTOT) toxicity and the immunosuppressive tumor microenvironment (TME). It incorporates a dual-component engineering strategy: a hypoxia-activated CAR that restricts T-cell activity to the hypoxic regions characteristic of tumors, and a constitutively expressed TGF-β chimeric switch receptor (CSR). The CSR is designed to bind soluble TGF-β within the TME and convert its typically immunosuppressive signal into a stimulatory one, thereby enhancing the cytotoxicity and persistence of the CAR T-cells. Preclinical results presented at AACR 2025 indicate that BTRPTB001L provides robust anti-tumor efficacy with an improved safety profile compared to standard hypoxia-responsive CAR T-cell designs.