Advances in the clinical application of bispecific antibodies in cancer therapy

Summary: Cancer immunotherapy has emerged as one of the most groundbreaking advancements. However, the tumor microenvironment (TME) is often dominated by various immunosuppressive factors, compromising the efficacy of single-target therapies, leading to non-responsiveness or resistance. Bispecific antibodies (BsAbs) represent an innovative immunotherapeutic strategy with enormous potential for improving cancer treatment outcomes. Unlike monoclonal antibodies, BsAbs can concurrently inhibit multiple pro-tumor pathways, target immune checkpoints to mitigate resistance, and bind to two distinct antigens, thereby enhancing specificity while minimizing off-target effects. Moreover, BsAbs are more cost-efficient and less toxic compared to the use of two separate monoclonal antibodies in combination. In recent decades, BsAbs have made remarkable progress in clinical development. Several BsAbs, such as blinatumomab, mosunetuzumab, teclistamab, glofitamab, epcoritamab, talquetamab, ivonescimab, cadonilimab, tarlatamab, zenocutuzumab, and catumaxomab, have achieved notable success in clinical trials. This review highlights clinically approved BsAbs and provides a comprehensive summary of their therapeutic applications in cancer treatment.