carbonic anhydrase IX CAR T-cells

Carbonic anhydrase IX (CAIX) CAR T-cells are an adoptive cell immunotherapy consisting of autologous or allogeneic T-cells genetically engineered to express a chimeric antigen receptor (CAR) specific for CAIX. CAIX is a cell-surface enzyme overexpressed in more than 90% of clear cell renal cell carcinomas (ccRCC) but has limited expression in normal tissues, making it a viable target for solid tumor CAR-T therapy. Early clinical development utilized first-generation constructs (e.g., G250), which encountered on-target off-tumor toxicities such as cholestatic liver injury due to low-level CAIX expression on bile duct epithelium. Subsequent research has focused on second-generation constructs incorporating costimulatory domains like CD28 or 4-1BB, as well as affinity-tuned CARs (e.g., G9) designed to selectively target high-density CAIX on tumor cells while sparing normal tissues. Current strategies also investigate combinations with tumor-targeted immunocytokines (e.g., Darleukin) to improve T-cell expansion and persistence within the immunosuppressive tumor microenvironment.

Other names

CAIX-targeted CAR-T cellsanti-CAIX CAR-T