A2B543

A2B543 is an investigational autologous CAR T-cell therapy developed by A2 Biotherapeutics for the treatment of adults with mesothelin (MSLN)-expressing solid tumors that have lost HLA-A*02 expression. The therapy is built on the proprietary Tmod™ platform, which utilizes logic-gate technology with dual receptors: an activator targeting MSLN on tumor cells and a blocker targeting HLA-A*02 on normal cells. This mechanism allows the CAR T-cells to selectively destroy tumor cells while sparing healthy tissue that retains HLA-A*02 expression. A2B543 is further enhanced with an inducible, membrane-tethered IL-12 (mem-IL-12) booster designed to increase potency and persistence within the immunosuppressive tumor microenvironment while minimizing systemic toxicity. It is currently being evaluated in the Phase 1/2 EVEREST-2 study for various solid tumors, including colorectal, pancreatic, non-small cell lung, and ovarian cancers, as well as mesothelioma.