RNA CART-meso

RNA CART-meso is an autologous chimeric antigen receptor (CAR) T-cell therapy developed by the University of Pennsylvania for the treatment of mesothelin-expressing solid tumors, including pancreatic ductal adenocarcinoma, malignant pleural mesothelioma, and ovarian cancer. Unlike traditional CAR-T therapies that utilize viral vectors for permanent transgene expression, RNA CART-meso employs mRNA electroporation to induce transient CAR expression in T cells. This approach was primarily designed as a safety measure to minimize the risk of sustained 'on-target, off-tumor' toxicity against normal tissues that express low levels of mesothelin, such as the pleura, pericardium, and peritoneum. The CAR construct typically incorporates an anti-mesothelin single-chain variable fragment (scFv) derived from the SS1 murine monoclonal antibody, linked to 4-1BB (CD137) costimulatory and CD3-zeta signaling domains. While clinical trials demonstrated the therapy's safety and feasibility across multiple infusions, the transient nature of CAR expression limited cellular persistence and long-term anti-tumor efficacy, prompting the development of second-generation lentiviral-based and humanized versions.

Other names

mRNA-engineered CART-mesomRNA-electroporated CART-mesomesothelin-specific RNA CAR T cells