Editors' ChoiceCancer

Two-in-One Antibody

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Science Signaling  24 Mar 2009:
Vol. 2, Issue 63, pp. ec108
DOI: 10.1126/scisignal.263ec108

Textbook definitions of antibodies emphasize the exquisite specificity with which these proteins bind their target antigens. New research suggests that this “one antibody–one antigen” paradigm can be tweaked in the laboratory. Working with an engineered library of variants of Herceptin, a therapeutic monoclonal antibody targeting the breast cancer growth factor HER2, Bostrom et al. (see Perspective by Parren and Burton) successfully selected variants that had antibody-combining sites that simultaneously bound with high affinity to a second cancer-relevant antigen, vascular endothelial growth factor (VEGF). In preliminary assays of efficacy, the two-in-one antibodies inhibited HER2- and VEGF-mediated cell proliferation in vitro, as well as tumor growth in mice, thus indicating the feasibility of a single therapeutic for cancer treatment.

J. Bostrom, S.-F. Yu, D. Kan, B. A. Appleton, C. V. Lee, K. Billeci, W. Man, F. Peale, S. Ross, C. Wiesmann, G. Fuh, Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323, 1610–1614 (2009). [Abstract] [Full Text]

P. W. H. I. Parren, D. R. Burton, Two-in-one designer antibodies. Science 323, 1567–1568 (2009). [Summary] [Full Text]