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

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Chames, P Hufton, SE Coulie, Pierre G. [UCL] Uchanska-Ziegler, B Hoogenboom, HR

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2000
Language Anglais
Journal information "Proceedings of the National academy of sciences of the United States of America" - Vol. 97, no. 14, p. 7969-7974 (2000)
Peer reviewed yes
Publisher National academy of sciences ((United States) [S.l.])
issn 0027-8424
e-issn 1091-6490
Publication status Publié
Affiliation UCL - Autre
Keywords phage display ; major histocompatibility complex ; T cell antigen receptor-like antibodies ; tumor targeting
Links
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Bibliographic reference Chames, P ; Hufton, SE ; Coulie, Pierre G. ; Uchanska-Ziegler, B ; Hoogenboom, HR. Direct selection of a human antibody fragment directed against the tumor T-cell epitope HLA-A1-MAGE-A1 from a nonimmunized phage-Fab library. In: Proceedings of the National academy of sciences of the United States of America, Vol. 97, no. 14, p. 7969-7974 (2000)
Permanent URL http://hdl.handle.net/2078.1/43441