Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence

Conventional immunotherapy has emerged as a key option for cancer treatment. However, its efficacy has been limited in urological cancers, especially prostate cancer, because of the immunosuppressive tumor microenvironment (TME), difficulty in drug delivery, aberrant immune response, and damage to normal cells. Bispecific antibodies (BsAbs) are engineered proteins with two different antigen-binding domains, designed using different technologies and in various formats. BsAb-based tumor immunotherapy has yielded optimistic results in preclinical and clinical investigations of many tumor types, including urological cancers. However, a series of challenges, including tumor heterogeneity, TME, Ab immunogenicity, adverse effects, serum half-life, low response rates, and drug resistance, hamper the application of BsAbs. In this review, we provide insights into the most common BsAb platforms with different mechanisms of action, which are under preclinical and clinical research, along with ways to overcome the challenges in BsAb administration for treating urological cancer.