Bispecific antibodies have emerged as a promising class of therapeutic agents in the field of cancer immunotherapy. As of August 2023, several bispecific antibodies were in various stages of development and clinical trials, showing great potential for improving cancer treatment outcomes.
One of the most notable bispecifics is blinatumomab (Blincyto), a CD19/CD3 bispecific approved for treating acute lymphoblastic leukemia (ALL) that has demonstrated impressive efficacy. Other promising candidates include mosunetuzumab and glofitamab, both targeting CD20 and CD3, which have shown promising results in non-Hodgkin’s lymphoma (NHL) trials. Odronextamab, another CD20/CD3 bispecific, is being evaluated for B-cell malignancies like NHL and chronic lymphocytic leukemia (CLL).
In the multiple myeloma space, cevostamab (FcRH5/CD3) and teclistamab (BCMA/CD3) have shown promise in clinical trials. Tarlatamab, a DLL3/CD3 bispecific, is being investigated for small cell lung cancer (SCLC) and other neuroendocrine tumors. For solid tumors, zenocutuzumab, a HER2/HER3 bispecific, is in trials for various indications, including breast, colorectal, and non-small cell lung cancers.
The unique feature of bispecific antibodies lies in their ability to simultaneously engage two different antigens, allowing them to bridge immune cells, particularly T cells, with tumor cells. This leads to enhanced tumor cell killing. Moreover, bispecifics can target tumor-associated antigens that are not easily addressable by conventional monoclonal antibodies or CAR-T cell therapies.
In addition to CD3-engaging bispecifics, other designs are being explored, such as those targeting immune checkpoints (e.g., PD-1, CTLA-4) or costimulatory receptors (e.g., 4-1BB, OX40) in combination with tumor antigens. Bispecifics are also being investigated in combination with other cancer therapies to enhance efficacy, overcome resistance, and improve patient outcomes.
While bispecific antibodies have shown impressive results in hematologic malignancies, their application in solid tumors remains an active area of research. Challenges such as tumor heterogeneity, immunosuppressive microenvironments, and on-target off-tumor toxicities need to be addressed to unlock their full potential in solid tumor indications.
As the field continues to advance, we can expect to see more innovative bispecific designs, optimized manufacturing processes, and novel target combinations. With ongoing clinical trials and preclinical research, bispecific antibodies hold great promise for revolutionizing cancer treatment in the coming years. However, their efficacy and safety profiles will need to be thoroughly evaluated in larger clinical trials before they can be widely adopted in clinical practice.
