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

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 Fc gamma receptors (Fc gamma Rs). These powerful approaches are being used to develop the next generation of cancer immunotherapeutics with improved efficacy and safety.

Automated summary

Agonist antibodies targeting immune checkpoints, especially those in the TNFR superfamily, are important for cancer treatment by regulating immune cell activity. However, their clinical utility is limited and antibody optimization is urgently needed to improve their therapeutic potential.