Unlocking the potential of agonist antibodies for treating cancer using antibody engineering

Harkamal S Jhajj; Timon S Lwo; Emily L Yao; Peter M Tessier

doi:10.1016/j.molmed.2022.09.012

Unlocking the potential of agonist antibodies for treating cancer using antibody engineering

Trends Mol Med. 2023 Jan;29(1):48-60. doi: 10.1016/j.molmed.2022.09.012. Epub 2022 Nov 4.

Authors

Harkamal S Jhajj¹, Timon S Lwo¹, Emily L Yao², Peter M Tessier³

Affiliations

¹ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
² Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
³ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: ptessier@umich.edu.

Abstract

Agonist antibodies that target immune checkpoints, such as those in the tumor necrosis factor receptor (TNFR) superfamily, are an important class of emerging therapeutics due to their ability to regulate immune cell activity, especially for treating cancer. Despite their potential, to date, they have shown limited clinical utility and further antibody optimization is urgently needed to improve their therapeutic potential. Here, we discuss key antibody engineering approaches for improving the activity of antibody agonists by optimizing their valency, specificity for different receptors (e.g., bispecific antibodies) and epitopes (e.g., biepitopic or biparatopic antibodies), and Fc affinity for Fcγ receptors (FcγRs). These powerful approaches are being used to develop the next generation of cancer immunotherapeutics with improved efficacy and safety.

Keywords: 4-1BB; CD137; CD40; OX40; immunotherapy; monoclonal antibody.

Publication types

Review

MeSH terms

Epitopes / therapeutic use
Humans
Immunotherapy
Neoplasms* / drug therapy
Neoplasms* / pathology

Substances

Epitopes

Abstract

Publication types

MeSH terms

Substances

Grants and funding