Carbonic Anhydrase IX: A Renewed Target for Cancer Immunotherapy.

The carbonic anhydrase isoform IX (CAIX) enzyme is constitutively overexpressed in the vast majority of clear cell renal cell carcinoma (ccRCC) and can also be induced in hypoxic microenvironments, a major hallmark of most solid tumors. CAIX expression is restricted to a few sites in healthy tissues, positioning this molecule as a strategic target for cancer immunotherapy. In this review, we summarized preclinical and clinical data of immunotherapeutic strategies based on monoclonal antibodies (mAbs), fusion proteins, chimeric antigen receptor (CAR) T, and NK cells targeting CAIX against different types of solid malignant tumors, alone or in combination with radionuclides, cytokines, cytotoxic agents, tyrosine kinase inhibitors, or immune checkpoint blockade.