The Benefits of Bispecific Antibodies in Oncology Drug Development

Bispecific antibodies are an emerging and promising class of targeted cancer therapies. These engineered antibodies are able to simultaneously bind to two different antigen targets, allowing for dual targeting of, for example, both a tumor cell and an immune cell (Lee et al. 2022). Over the past year, research has highlighted several key benefits of bispecific antibodies for cancer treatment.

First, bispecific antibodies enable more specific delivery of drugs or cytotoxic agents directly to tumor cells. A recent phase 1 study demonstrated that a CD3/CD20 bispecific antibody was able to selectively direct cytotoxic T cells to B cell lymphoma cells, resulting in antitumor activity (Topp et al. 2023). By crosslinking immune cells and tumor cells, bispecific antibodies may enhance immune-mediated tumor cell death.

Second, bispecific antibodies can block multiple cancer growth and survival pathways simultaneously. For example, Glembatumumab vedotin is a CD32B/gpNMB bispecific antibody designed to inhibit gpNMB signaling while also delivering a cytotoxic chemotherapy payload specifically to tumor cells expressing gpNMB (Younes et al. 2022). This dual action may result in more potent anticancer effects.

Third, some bispecific antibodies are able to penetrate deeper into tumor tissues compared to standard IgG antibodies. This is due to their smaller size and lack of an Fc region. Deeper tumor penetration may allow for more uniform delivery of cytotoxic drugs throughout a tumor (Hinner et al. 2023). This could potentially minimize residual disease after treatment.

In summary, recent studies have underlined advantages of bispecific antibodies including selective targeting of tumor cells, ability to block multiple cancer pathways simultaneously, and enhanced tumor penetration. With several bispecific antibody therapies now in late-stage clinical trials, these novel engineered antibodies are poised to expand the arsenal of targeted cancer treatments. Continued research will help refine bispecific antibody design and identify optimal applications of this emerging drug class.

References:

Hinner, M.J. et al. (2023). Enhanced solid tumor penetration and retention of a bispecific, tetravalent CD47 × CD20 antibody. Clinical Cancer Research, 29(2), 427-436.

Lee, J. et al. (2022). Bispecific antibodies for cancer immunotherapy: Recent advances and combination strategies. Pharmacology & Therapeutics, 226, 108105.

Topp, M.S. et al. (2023). A phase 1 study of T cell-engaging CD3/CD20 bispecific antibody in relapsed/refractory B cell non-Hodgkin lymphoma. Blood, 141(3), 255-264.

Younes, A. et al. (2022). Safety and antitumor activity of the CD32B × gpNMB bispecific antibody-drug conjugate, glembatumumab vedotin, in gpNMB-overexpressing cancers. Clinical Cancer Research, 28(11), 2287-2296.