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

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.

[1]  C. Janeway,et al.  A novel MHC class II epitope expressed in thymic medulla but not cortex , 1989, Nature.

[2]  S. Kurtzman,et al.  Enhancement of cytolytic T lymphocyte precursor frequency in melanoma patients following immunization with the MAGE-1 peptide loaded antigen presenting cell-based vaccine. , 1996, Cancer research.

[3]  C. Seitz,et al.  The monoclonal antibody HCA2 recognises a broadly shared epitope on selected classical as well as several non-classical HLA class I molecules. , 1998, Molecular immunology.

[4]  A. Chang,et al.  Clinical implications of the new biology in the development of melanoma vaccines , 1999, Journal of surgical oncology.

[5]  R. Steinman,et al.  High Levels of a Major Histocompatibility Complex II–Self Peptide Complex on Dendritic Cells from the T Cell Areas of Lymph Nodes , 1997, The Journal of experimental medicine.

[6]  J. Zeuthen,et al.  Recognition of insulin on MHC-class-II-expressing L929 cells by antibody and T cells. , 1989, Research in immunology.

[7]  P. Coulie,et al.  Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE‐3 and presented by HLA‐A1 , 1999, International journal of cancer.

[8]  L. Fugger,et al.  Recombinant antibodies with the antigen-specific, MHC restricted specificity of T cells: novel reagents for basic and clinical investigations and immunotherapy. , 1999, Immunotechnology : an international journal of immunological engineering.

[9]  J. Arends,et al.  Human single-chain Fv antibodies to MUC1 core peptide selected from phage display libraries recognize unique epitopes and predominantly bind adenocarcinoma. , 1998, Cancer research.

[10]  D. Wiley,et al.  HLA-A2-peptide complexes: refolding and crystallization of molecules expressed in Escherichia coli and complexed with single antigenic peptides. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Davies,et al.  A scanning tunnelling microscopy comparison of passive antibody adsorption and biotinylated antibody linkage to streptavidin on microtiter wells. , 1994, Journal of immunological methods.

[12]  R. Arnon,et al.  Immunomodulation of experimental allergic encephalomyelitis by antibodies to the antigen–Ia complex , 1991, Nature.

[13]  J. Ozols,et al.  Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. Wraith,et al.  Searching for MHC‐restricted anti‐viral antibodies: antibodies recognizing the nucleoprotein of influenza virus dominate the serological response of C57BL/6 mice to syngeneic influenza‐infected cells , 1987, European journal of immunology.

[15]  D. Stuart,et al.  Production, crystallization, and preliminary X‐ray analysis of the human MHC class Ib molecule HLA‐E , 1998, Protein science : a publication of the Protein Society.

[16]  A. Plückthun,et al.  Correctly folded T-cell receptor fragments in the periplasm of Escherichia coli. Influence of folding catalysts. , 1994, Journal of molecular biology.

[17]  P. Cresswell,et al.  Mechanisms of MHC class I--restricted antigen processing. , 1998, Annual review of immunology.

[18]  H R Hoogenboom,et al.  Designing and optimizing library selection strategies for generating high-affinity antibodies. , 1997, Trends in biotechnology.

[19]  P. A. Peterson,et al.  Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. , 1994, Science.

[20]  M. Weijtens,et al.  Single chain Ig/gamma gene-redirected human T lymphocytes produce cytokines, specifically lyse tumor cells, and recycle lytic capacity. , 1996, Journal of immunology.

[21]  G. Cornelis,et al.  Identification of five MAGE-A1 epitopes recognized by cytolytic T lymphocytes obtained by in vitro stimulation with dendritic cells transduced with MAGE-A1. , 1999, Journal of immunology.

[22]  P. Chomez,et al.  A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. , 1991, Science.

[23]  P. S. Andersen,et al.  A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Butler,et al.  The physical and functional behavior of capture antibodies adsorbed on polystyrene. , 1992, Journal of immunological methods.

[25]  J. Yewdell,et al.  Direct delivery of exogenous MHC class I molecule-binding oligopeptides to the endoplasmic reticulum of viable cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. Lidholm,et al.  BIACORE analysis of histidine-tagged proteins using a chelating NTA sensor chip. , 1997, Analytical biochemistry.

[27]  E. Unanue,et al.  Characterization and quantitation of peptide-MHC complexes produced from hen egg lysozyme using a monoclonal antibody. , 1997, Immunity.

[28]  E. Meinl,et al.  Refolding of human class II major histocompatibility complex molecules isolated from Escherichia coli. Assembly of peptide-free heterodimers and increased refolding-yield in the presence of antigenic peptide. , 1994, The Journal of biological chemistry.

[29]  J. Kirkwood,et al.  New treatment options for patients with melanoma: review of melanoma-derived T-cell epitope-based peptide vaccines , 1996, Melanoma research.

[30]  P. Ebbesen,et al.  Expression of HLA class I molecules in human first trimester and term placenta trophoblast , 1996, Cell and Tissue Research.

[31]  A. Rudensky,et al.  Major Histocompatibility Complex Class II Compartments in Human and Mouse B Lymphoblasts Represent Conventional Endocytic Compartments , 1997, The Journal of cell biology.

[32]  R. Coleman,et al.  The potential of melanoma antigen expression in cancer therapy. , 1999, Cancer treatment reviews.

[33]  Hennie R. Hoogenboom,et al.  A Large Non-immunized Human Fab Fragment Phage Library That Permits Rapid Isolation and Kinetic Analysis of High Affinity Antibodies* , 1999, The Journal of Biological Chemistry.

[34]  B. Groner,et al.  Cytolysis of tumor cells expressing the Neu/erbB-2, erbB-3, and erbB-4 receptors by genetically targeted naive T lymphocytes. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[35]  R. Germain,et al.  Production, specificity, and functionality of monoclonal antibodies to specific peptide-major histocompatibility complex class II complexes formed by processing of exogenous protein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[36]  D. Hicklin,et al.  beta2-Microglobulin mutations, HLA class I antigen loss, and tumor progression in melanoma. , 1998, The Journal of clinical investigation.

[37]  P. Romero,et al.  HLA Photoaffinity Labeling Reveals Overlapping Binding of Homologous Melanoma-associated Gene Peptides by HLA-A1, HLA-A29, and HLA-B44 (*) , 1996, The Journal of Biological Chemistry.

[38]  L. Terracciano,et al.  © 1999 Cancer Research Campaign Article no. bjoc.1999.0810 Expression of MAGE-1 and-3 genes and gene products in human hepatocellular carcinoma , 2022 .

[39]  A. Rudensky,et al.  A study of complexes of class II invariant chain peptide: Major histocompatibility complex class II molecules using a new complex‐specific monoclonal antibody , 1996, European journal of immunology.

[40]  R. Tampé,et al.  Reduced membrane major histocompatibility complex class I density and stability in a subset of human renal cell carcinomas with low TAP and LMP expression. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[41]  A. McMichael,et al.  Tetrameric Complexes of Human Histocompatibility Leukocyte Antigen (HLA)-G Bind to Peripheral Blood Myelomonocytic Cells , 1999, The Journal of experimental medicine.

[42]  B. Nag,et al.  Refolding and Reconstitution of Functionally Active Complexes of Human Leukocyte Antigen DR2 and Myelin Basic Protein Peptide from Recombinant and Polypeptide Chains (*) , 1995, The Journal of Biological Chemistry.

[43]  G. Fleuren,et al.  T-cell based cancer immunotherapy: direct or redirected tumor-cell recognition? , 1994, Immunology today.

[44]  K. Parker,et al.  Peptide binding to HLA-A2 and HLA-B27 isolated from Escherichia coli. Reconstitution of HLA-A2 and HLA-B27 heavy chain/beta 2-microglobulin complexes requires specific peptides. , 1992, The Journal of biological chemistry.

[45]  C. Barnstable,et al.  Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis , 1978, Cell.

[46]  I. Pastan,et al.  Peptide-specific killing of antigen-presenting cells by a recombinant antibody-toxin fusion protein targeted to major histocompatibility complex/peptide class I complexes with T cell receptor-like specificity. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[47]  T. Clackson,et al.  Making antibody fragments using phage display libraries , 1991, Nature.

[48]  J. Yewdell,et al.  Localization, quantitation, and in situ detection of specific peptide-MHC class I complexes using a monoclonal antibody. , 1997, Immunity.

[49]  R. Arnon,et al.  Modulation of the immune response in multiple sclerosis: production of monoclonal antibodies specific to HLA/myelin basic protein. , 1997, Journal of immunology.

[50]  A. Rudensky,et al.  Monoclonal antibody detection of a major self peptide. MHC class II complex. , 1992, Journal of immunology.

[51]  Catia,et al.  A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E , 1992, The Journal of experimental medicine.

[52]  R. Germain,et al.  Antigen-unspecific B Cells and Lymphoid Dendritic Cells Both Show Extensive Surface Expression of Processed Antigen–Major Histocompatibility Complex Class II Complexes after Soluble Protein Exposure In Vivo or In Vitro , 1997, The Journal of experimental medicine.

[53]  H R Hoogenboom,et al.  By-passing immunization. Human antibodies from V-gene libraries displayed on phage. , 1991, Journal of molecular biology.