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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.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2000 Jul 05; Vol. 97 (14), pp. 7969-74. - Publication Year :
- 2000
-
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 MAGE-A1 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.
- Subjects :
- Antigen Presentation
Antigens, Differentiation
Antigens, Neoplasm
Biosensing Techniques
Cloning, Molecular
Epitopes
Flow Cytometry
HLA-A1 Antigen isolation & purification
Humans
Melanoma-Specific Antigens
Neoplasm Proteins isolation & purification
Peptide Library
Protein Folding
Selection, Genetic
Antibodies, Neoplasm genetics
HLA-A1 Antigen immunology
Immunoglobulin Fab Fragments genetics
Melanoma immunology
Neoplasm Proteins immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 97
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 10884427
- Full Text :
- https://doi.org/10.1073/pnas.97.14.7969