Bispecific Antibodies Reach the Clinic, With More Advances Ahead

Robert L. Ferris, MD, PhD

Director

Hillman Cancer Center

University of Pittsburgh

Medical Center

Pittsburgh, PA

As we take in the exciting new advances discussed at the recent 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, this column again acknowledges the novel therapeutic agents being developed. Over the years, we have reflected on the excitement of immune checkpoint inhibitors, which are now approved for most cancers in various stages. We also celebrated the successes of cellular therapies in solid and liquid tumors. The concept of so-called designer antibody therapies was proposed, and protein engineering launched—based on the rapidly improving understanding of biology and emergence of new therapeutic targets.

These agents are finally being used in clinical practice. There is a whole synthetic engineering strategy to developing an antibody with dual specifi cities, similar to the concept of antibody-drug conjugates. The antibody specificity may attract and colocalize different cell populations or simply take advantage of multiple targets being expressed on the same tumor cell. In some situations, bispecific antibodies may actually be so effective as to replace the more complex cellular production of a chimeric antigen receptor and tumor-infiltrating lymphocyte therapy.

Further enhancement of these bispecific antibodies may be to retain effector function of the antibody itself and trigger extrinsic cellular immune stimulation in the tumor microenvironment. Indeed, the specificity variability of the novel antibody molecule may create a local tumor microenvironment that is part of the appeal.

Although some of these protein engineering strategies may have seemed far off, we have seen in the past months beneficial activity with an off-the-shelf advantage over long-production personalized cellular therapy. Because antibody therapies have been broadly used across solid tumors and chimeric antigen receptor T-cell therapies are so far restricted to lymphoid and blood cancers, the expanse of oncology that may be impacted by these novel bispecific antibodies and their derivatives is truly exciting, and their effect may be transformative.

Emerging from the ASCO meeting and looking toward European Society for Medical Oncology Congress, I expect that we will see more and more of these advances. What an exciting time and motivation for further investment in collaboration between academia and industry, in partnership with patients and governmental investigational mechanisms.