Bispecific Antibodies in Glioblastoma: Mechanistic Advances, Delivery Innovations, and Translational Challenges in Overcoming Immune Escape

The application of bispecific antibody (BsAbs)-based therapeutic strategies for glioblastoma (GBM) has shown considerable promise. By concurrently targeting tumor-associated antigens and immune effector cells, BsAbs can traverse the blood-brain barrier, modulate the immunosuppressive tumor microenvironment, and surmount challenges such as intratumoral heterogeneity and immune evasion. Accumulating evidence indicates that BsAbs surpass conventional monoclonal antibodies and chimeric antigen receptor T cell therapies in the context of GBM through mechanisms that include the redirection of immune cells, blockade of immune checkpoints, and synergistic inhibition of oncogenic signaling pathways. Although constrained by limitations in intracerebral delivery efficiency and the potential for immune-related adverse events, BsAbs represent a promising new frontier in GBM immunotherapy. They particularly enhance therapeutic precision and durability, underscoring their potential as a transformative approach for managing this aggressive malignancy.