Craig L. Slingluff, Jr., MD
Immunotherapy clinical trials with peptide vaccines
The main focus of our laboratory is the identification of human tumor antigens recognized by human cytotoxic T-lymphocytes (CTL), in the elucidating the nature of the host: tumor relationship and in hopes of creating novel immunologic treatments for human cancer. We use human tumor cells and autologous lymphocytes to generate tumor specific CTL, HLA-type the patient's cells, seek evidence of shared tumor antigens, and extract MHC-associated peptides. In collaboration with Drs. Engelhard and Hunt, immunologically active peptides are identified and sequenced using tandem mass spectrometry. At present, most of our energies are devoted to identification of peptide epitopes for CTL specific for human melanoma expressing HLA-A2.1. We have recently identified one peptide epitope for HLA-A2-restricted melanoma-specific CTL, and we poised to identify others. We are preparing tumor vaccines in the laboratory, using melanoma cell lines as well as synthetic peptides, and a major effort in the lab will be to evaluate patient immune responses to novel tumor vaccines. The work is being expanded to include identification of peptide epitopes for melanoma presented on HLA-A3 and on other MHC molecules, as well as the identification of peptide epitopes for CTL specific for solid tumors other than melanoma. We have human CTL lines specific for melanoma and restricted HLA-A3 and other CTLl ines specific for squamous cell carcinoma of the lung. We have preliminary data on CTL against colon, ovarian, and breast cancers. The process of peptide extraction and identification is well underway for the characterization of epitopes from the HLA-A3(+) melanomas and from lung cancer.