Targeting cancer with bispecific antibodies

Protein-based immunotherapies offer the possibility of generic or “off-the-shelf” immunotherapies, different from the highly personalized approach of engineered immune cell therapies. For example, T cell–engaging bispecific antibodies (CD3 BsAbs) trigger signaling of the CD3 surface receptor on T cells and also bind to a second target protein on tumor cells, thereby activating cytotoxic T cells to eliminate cancer cells with one antibody molecule. But this approach has challenges, including identifying shared cancer-selective targets and protein engineering to redirect T cells. A study by Hsiue et al. (1) on page 1009 of this issue and a study by Douglass et al. (2) describe the development of CD3 BsAbs that recognize mutation-associated neoantigens (MANAs). Additionally, Paul et al. (3) describe a CD3 BsAb that uses T cell receptor (TCR)–specific antibodies to selectively eliminate T cell malignancies. In the future, these immunotherapeutic agents could be used to treat diverse cancers with specific mutations.