Direct selection of a human antibody fragment directed against the tumor T-cell epitope HLA-A1-MAGE-A1 from a nonimmunized phage-Fab library

Chames, P;Hufton, SE;Coulie, Pierre;Uchanska-Ziegler, B;Hoogenboom, HR
(2000) Proceedings of the National academy of sciences of the United States of America — Vol. 97, n° 14, p. 7969-7974 (2000)

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Authors
  • Chames, P
    Author
  • Hufton, SE
    Author
  • Coulie, Pierreorcid-logoUCLouvain
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  • Uchanska-Ziegler, B
    Author
  • Hoogenboom, HR
    Author
Abstract
Antitumor antibodies with the same specificity as cytotoxic T lymphocytes that recognize antigenic peptides encoded by tumor-associated genes and presented by MHC class I molecules would be valuable tools to analyze the antigenicity or target tumor cells in vivo. To obtain a human antibody directed against a peptide encoded by gene melanoma-associated antigen (MAGE)-A1 and presented by HLA-A1 molecules, we selected a large phage Fab antibody repertoire on a recombinant version of the complex HLA-A1-MAGE-A1 produced by in vitro refolding. One of the selected phage antibodies shows binding to HLA-A1 complexed with the MAGE-A1 peptide, but does not show binding to HLA-A1 complexed with a peptide encoded by gene MAGE-A3 and differing from the MAGE-A1 peptide by only three residues. Phages carrying this recombinant antibody bind to HLA-A1(+) cells only after in vitro loading with MACE-Al peptide. These results indicate that nonimmunized phage Fab libraries are a source of antibodies with a T cell antigen receptor-like specificity. The human anti-HLA-A1-MAGE-A1 antibody described here may prove very useful for monitoring the cell surface expression of these complexes, and eventually, as a targeting reagent for the specific immunotherapy of HLA-A1 patients bearing a MAGE-A1-positive tumor.
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Chames, P., Hufton, S., Coulie, P., Uchanska-Ziegler, B., & Hoogenboom, H. (2000). Direct selection of a human antibody fragment directed against the tumor T-cell epitope HLA-A1-MAGE-A1 from a nonimmunized phage-Fab library. Proceedings of the National academy of sciences of the United States of America, 97(14), 7969-7974. https://doi.org/10.1073/pnas.97.14.7969 (Original work published 2000)