Unlocking precision: Bispecific T cell engagers and the next frontier in uro-oncology

Urological cancers, including prostate, bladder, renal, and testicular cancers, present significant challenges in terms of incidence, mortality, and treatment resistance. Immunotherapy, particularly bispecific T-cell engagers (BiTEs), has emerged as a promising therapeutic strategy, targeting tumor-specific antigens to activate T cells and enhance anti-tumor immunity. BiTEs, such as pasotuxizumab for prostate cancer, and CD3 ×B7-H3 BiTE for bladder cancer, demonstrate potential in overcoming the limitations of traditional therapies and immune checkpoint inhibitors. This review explores the application of BiTEs in urological cancers, highlighting their clinical outcomes, challenges, and future prospects. Although BiTEs offer significant advantages, including selective T-cell activation and low-dose efficacy, obstacles such as on-target off-tumor toxicity, the immunosuppressive tumour microenvironment (TME), and immune-related adverse effects need to be addressed for broader clinical success. Combination therapies with immune checkpoint inhibitors and oncolytic viruses, as well as advancements in BiTE technology, are essential to improving treatment efficacy. The future of BiTEs in uro-oncology lies in overcoming current limitations, optimising therapeutic strategies, and expanding clinical trials to solidify their role in cancer immunotherapy. [Abstract copyright: Copyright © 2025 Elsevier B.V. All rights reserved.]