Mesothelin biology and the evolving landscape of targeted immunotherapy

Due to its restricted expression in normal tissues, its frequent overexpression in various aggressive malignancies, and its involvement in several pro-tumorigenic signaling pathways, mesothelin, a glycosylphosphatidylinositol-anchored cell surface protein, has been identified as a promising tumor-associated antigen. This review provides an up-to-date comprehensive overview regarding the role of mesothelin in cancer. It encompasses the protein structural characteristics, expression profiles, glycosylation patterns, shedding mechanisms, prognostic significance, and functional roles. Subsequently, therapeutic strategies targeting mesothelin that have advanced to clinical trial stage are discussed, including vaccine-based approaches, antibody-mediated immunotherapies, and cell therapies. The remaining challenges of mesothelin targeted treatments are highlighted, along with the ongoing options aimed at overcoming these limitations.