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-pept ide tetramer on tumor cells can render them susceptible to lysis by relevan t cytotoxic T lymphocytes (CTL), biotinylated HLA-A*0201/Flu matrix peptide complexes were tetramerized on streptavidin molecules previously coupled t o Fab' fragments from monoclonal antibodies (mAb) specific for cell surface markers such as carcinoembryonic antigen (CEA), ErbB-2 or CD20. Flow cytom etry analysis showed that coating of the HLA-A2-peptide complexes on the fo ur HLA-A2-negative human cancer lines tested (including a CEA-positive colo n carcinoma, an ErbB-2(+) breast carcinoma and two CD20(+) B lymphomas) was entirely dependent upon the specificity of the conjugated antibody fragmen ts. More importantly, HLA-A2-restricted Flu matrix peptide-specific CTL wer e then found to lyse specifically and efficiently the MHC-coated target cel ls. These results open the way to the development of new immunotherapy stra tegies based on antibody targeting of MHC class I-peptide complexes.