Research ArticleCancer

Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3

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Science Translational Medicine  17 Oct 2018:
Vol. 10, Issue 463, eaat5775
DOI: 10.1126/scitranslmed.aat5775

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Less can be more for tumor targeting

HER2 is a receptor tyrosine kinase that is often overexpressed in breast cancer. Unfortunately, many normal tissues also express HER2, resulting in toxicity from HER2-targeted treatments. Slaga et al. have developed a T cell–dependent bispecific antibody that binds to both HER2 and the CD3 protein on T cells, helping redirect the T cells to recognize tumor cells. To improve treatment safety, the authors selected an antibody that binds two HER2 molecules at a time, but with low affinity for each one, making it selective for tumors that have a high density of surface HER2 relative to healthy tissues.