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

被引:92
作者
Chames, P
Hufton, SE
Coulie, PG
Uchanska-Ziegler, B
Hoogenboom, HR
机构
[1] Maastricht Univ, Dept Pathol, NL-6202 AZ Maastricht, Netherlands
[2] Univ Hosp Maastricht, NL-6202 AZ Maastricht, Netherlands
[3] Target Quest BV, Provisorium, NL-6202 AZ Maastricht, Netherlands
[4] Catholic Univ Louvain, Cellular Genet Unit, B-1200 Brussels, Belgium
[5] Humboldt Univ, Univ Klinikum charite, Inst Immungenet, D-14050 Berlin, Germany
关键词
phage display; major histocompatibility complex; T cell antigen receptor-like antibodies; tumor targeting;
D O I
10.1073/pnas.97.14.7969
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:7969 / 7974
页数:6
相关论文
共 57 条
  • [1] IMMUNOMODULATION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY ANTIBODIES TO THE ANTIGEN-IA COMPLEX
    AHARONI, R
    TEITELBAUM, D
    ARNON, R
    PURI, J
    [J]. NATURE, 1991, 351 (6322) : 147 - 150
  • [2] Tetrameric complexes of human histocompatibility leukocyte antigen (HLA)-G bind to peripheral blood myelomonocytic cells
    Allan, DSJ
    Colonna, M
    Lanier, LL
    Churakova, TD
    Abrams, JS
    Ellis, SA
    McMichael, AJ
    Braud, VM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (07) : 1149 - 1155
  • [3] Altenschmidt U, 1996, CLIN CANCER RES, V2, P1001
  • [4] A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells
    Andersen, PS
    Stryhn, A
    Hansen, BE
    Fugger, L
    Engberg, J
    Buus, S
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (05) : 1820 - 1824
  • [5] REFOLDING AND RECONSTITUTION OF FUNCTIONALLY ACTIVE COMPLEXES OF HUMAN-LEUKOCYTE ANTIGEN-DR2 AND MYELIN BASIC-PROTEIN PEPTIDE FROM RECOMBINANT-ALPHA AND RECOMBINANT-BETA POLYPEPTIDE-CHAINS
    ARIMILLI, S
    CARDOSO, C
    MUKKU, P
    BAICHWAL, V
    NAG, B
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (02) : 971 - 977
  • [6] PRODUCTION OF MONOCLONAL ANTIBODIES TO GROUP-A ERYTHROCYTES, HLA AND OTHER HUMAN CELL-SURFACE ANTIGENS - NEW TOOLS FOR GENETIC-ANALYSIS
    BARNSTABLE, CJ
    BODMER, WF
    BROWN, G
    GALFRE, G
    MILSTEIN, C
    WILLIAMS, AF
    ZIEGLER, A
    [J]. CELL, 1978, 14 (01) : 9 - 20
  • [7] T-CELL BASED CANCER-IMMUNOTHERAPY - DIRECT OR REDIRECTED TUMOR-CELL RECOGNITION
    BEUN, GDM
    VANDEVELDE, CJH
    FLEUREN, GJ
    [J]. IMMUNOLOGY TODAY, 1994, 15 (01): : 11 - 15
  • [8] THE PHYSICAL AND FUNCTIONAL-BEHAVIOR OF CAPTURE ANTIBODIES ADSORBED ON POLYSTYRENE
    BUTLER, JE
    NI, L
    NESSLER, R
    JOSHI, KS
    SUTER, M
    ROSENBERG, B
    CHANG, J
    BROWN, WR
    CANTARERO, LA
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 1992, 150 (1-2) : 77 - 90
  • [9] Chaux P, 1999, J IMMUNOL, V163, P2928
  • [10] MAKING ANTIBODY FRAGMENTS USING PHAGE DISPLAY LIBRARIES
    CLACKSON, T
    HOOGENBOOM, HR
    GRIFFITHS, AD
    WINTER, G
    [J]. NATURE, 1991, 352 (6336) : 624 - 628