Molecular understanding and clinical aspects of adoptive cellular immunotherapy in prostate cancer

Adoptive cellular immunotherapy (ACT) is a milestone therapeutic strategy that directly eliminates tumor cells or enhances anti-tumor immunity through the infusion of activated and expanded autologous lymphocytes in vitro. ACT has shown great potential as a treatment strategy for diverse malignant hematopoietic tumors. However, in solid tumors, this success has not been replicated due to the immunosuppressive mechanism within the tumor microenvironment (TME), low tumor antigenicity, infiltration of suppressive immune cells, and the emergence of severe adverse events (AEs). In recent years, chimeric antigen receptor T cells (CAR-T), T-cell receptor-engineered T cells (TCR-T), chimeric antigen receptor natural killer cells (CAR-NK), bispecific T-cell engagers (BiTEs), and CAR-macrophages (CAR-M) have been extensively investigated, and are expected to offer improved safety, feasibility and therapeutic efficacy in solid tumors. Prostate cancer (PCa) is initially androgen dependent. However, once the disease progresses to metastatic castration-resistant PCa (mCRPC) and drug resistance occurs, current treatments often fail to achieve satisfactory outcomes. As an immunotherapeutic approach, ACT offers a novel therapeutic concept for the treatment of mCRPC. This review presents a comprehensive overview of the development and mechanisms of various ACT strategies, with the aim of providing a theoretical and experimental basis for future therapeutic development.