In comparison to haematological malignancies, redirecting T cell activity to eradicate solid tumours has proved challenging, primarily owing to the lack of tumour-restricted antigens. Here, Slaga et al. develop an anti-HER2/CD3 T cell–dependent bispecific (TDB) antibody that selectively targets HER2-overexpressing tumour cells relative to healthy cells, owing to the presence of two low-affinity anti-HER2 Fab arms. A single intravenous dose of the antibody potently induced regression of HER2-overexpressing tumours in mouse xenograft models. Importantly, the antibody displayed limited pharmacological activity in cynomolgus monkey tissues and was well-tolerated.
References
Slaga, D. et al. Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3. Sci. Transl Med. 10, eaat5775 (2018)
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Crunkhorn, S. Redirecting T cell activity in solid tumours. Nat Rev Drug Discov 17, 864 (2018). https://doi.org/10.1038/nrd.2018.214
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DOI: https://doi.org/10.1038/nrd.2018.214
