Abstract
Bispecific antibodies (bsAbs) enable novel mechanisms of action and/or therapeutic applications that cannot be achieved using conventional IgG-based antibodies. Consequently, development of these molecules has garnered substantial interest in the past decade and, as of the end of 2023, 14 bsAbs have been approved: 11 for the treatment of cancer and 3 for non-oncology indications. bsAbs are available in different formats, address different targets and mediate anticancer function via different molecular mechanisms. Here, we provide an overview of recent developments in the field of bsAbs for cancer therapy. We focus on bsAbs that are approved or in clinical development, including bsAb-mediated dual modulators of signalling pathways, tumour-targeted receptor agonists, bsAb–drug conjugates, bispecific T cell, natural killer cell and innate immune cell engagers, and bispecific checkpoint inhibitors and co-stimulators. Finally, we provide an outlook into next-generation bsAbs in earlier stages of development, including trispecifics, bsAb prodrugs, bsAbs that induce degradation of tumour targets and bsAbs acting as cytokine mimetics.
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Acknowledgements
The authors thank all contributors, team members and collaborators involved in the field of bispecific antibodies (bsAbs) over the past decade. In the context of bsAbs, C.K. thanks P. Umana, Roche Innovation Center Zurich and all his colleagues at the Roche Innovation Centers in Zurich, Munich and Basel and Wolfgang Schaefer, Mannheim. The authors thank I. Wiesner, Roche Diagnostics GmbH, Penzberg, for help with antibody databases. The authors apologize to those authors whose work was overseen by error or could not be cited due to space limitation and the breadth of the field, or due to the unavailability of peer-reviewed manuscripts.
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C.K., U.B., J.M.R. and R.E.K. researched data for the article and wrote the article. All authors contributed substantially to discussion of the content and edited the manuscript before submission.
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C.K. and U.B. declare employment, stock ownership and patents/royalties with Roche. J.M.R. is employed by The Antibody Society, a non-profit trade association funded by corporate sponsors that develops antibody therapeutics or provides services to companies that develop antibody therapeutics, and is Editor-in-Chief of mAbs, a biomedical journal focused on topics relevant to antibody therapeutic development. R.E.K. is a consultant for Immatics, Roche, SunRock and Oncomatryx.
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Klein, C., Brinkmann, U., Reichert, J.M. et al. The present and future of bispecific antibodies for cancer therapy. Nat Rev Drug Discov 23, 301–319 (2024). https://doi.org/10.1038/s41573-024-00896-6
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DOI: https://doi.org/10.1038/s41573-024-00896-6
