Antibody-conjugated MHC class I tetramers can target tumor cells for specific lysis by T lymphocytes.
To demonstrate that antibody-guided targeting of antigenic MHC class I-peptide tetramer on tumor cells can render them susceptible to lysis by relevant cytotoxic T lymphocytes (CTL), biotinylated HLA-A*0201/Flu matrix peptide complexes were tetramerized on streptavidin molecules previously coupled to Fab' fragments from monoclonal antibodies (mAb) specific for cell surface markers such as carcinoembryonic antigen (CEA), ErbB-2 or CD20. Flow cytometry analysis showed that coating of the HLA-A2-peptide complexes on the four HLA-A2-negative human cancer lines tested (including a CEA-positive colon carcinoma, an ErbB-2(+) breast carcinoma and two CD20(+) B lymphomas) was entirely dependent upon the specificity of the conjugated antibody fragments. More importantly, HLA-A2-restricted Flu matrix peptide-specific CTL were then found to lyse specifically and efficiently the MHC-coated target cells. These results open the way to the development of new immunotherapy strategies based on antibody targeting of MHC class I-peptide complexes.
Robert
B
B
Biochemistry Institute, University of Lausanne, Epalinges, Switzerland.
Guillaume
P
P
Luescher
I
I
Romero
P
P
Mach
J P
JP
D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates; D007167:Immunotherapy; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D018796:Immunoconjugates