Cellular therapies have revolutionized the treatment landscape for hematologic and solid malignancies, offering highly targeted approaches that harness the immune system’s power. Two of the most promising modalities in this field are bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) therapy, each with unique mechanisms of action and therapeutic potential.

 

Bispecific antibodies are engineered molecules designed to simultaneously bind to two different antigens. Most commonly, one arm targets a tumor-associated antigen, such as CD19 or BCMA, while the other engages CD3 on T cells, effectively bridging the immune effector cell to the tumor cell. This dual engagement triggers T-cell activation, proliferation, and cytotoxicity specifically at the site of the tumor, minimizing off-target effects. Bispecific antibodies, such as blinatumomab for B-cell malignancies and teclistamab/elranatamab for multiple myeloma, have demonstrated remarkable efficacy, especially in patients with relapsed or refractory disease. Their off-the-shelf availability and lower cost compared to autologous therapies provide a logistical advantage, although cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain significant adverse effects that require careful management.

 

CAR-T cell therapy, on the other hand, involves genetic modification of a patient’s own T cells to express a chimeric antigen receptor that can recognize and destroy tumor cells. Approved CAR-T therapies, such as tisagenlecleucel and axicabtagene ciloleucel, have achieved durable remissions in aggressive malignancies like acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma. This personalized approach allows for precision targeting of tumor antigens while bypassing the need for major histocompatibility complex (MHC) presentation. Despite its transformative impact, CAR-T therapy faces challenges, including manufacturing complexities, high costs, and the risk of severe toxicities such as CRS, ICANS, and prolonged cytopenias. Efforts to develop allogeneic CAR-T cells, which use donor T cells instead of autologous cells, are underway to overcome these barriers.

 

Both bispecific antibodies and CAR-T therapies represent significant advancements in cancer treatment. Ongoing research aims to optimize their safety profiles, expand their applicability to solid tumors, and explore combinatory approaches with other immunotherapies or conventional treatments. As our understanding of tumor biology and immune interactions deepens, these therapies will likely continue to evolve, bringing new hope to patients with otherwise limited options.