Proteomic Footprinting of Drug-Treated Cancer Cells as a Measure of Cellular Vaccine Efficacy for the Prevention of Cancer Recurrence

The comparative proteomic study of cell surfaces of native and drug-treated cancer cells was performed. To this end, cell proteomic footprinting, which reflects the mass spectrometry profiling of cell surface proteins, was applied to breast adenocarcinoma cells (MCF-7), which were untreated or treated with doxorubicin, tamoxifen, or etoposide. The footprints of drug-treated cells were compared with the footprints of untreated cells and the footprint of a randomly selected control cancer cell culture. It was found that drug-treated cells have reproducible, pronounced, and drug-specific changes in cell surface protein expression. Cytotoxicity assays, which are an in vitro model of human antitumor vaccination, revealed that the degree of these changes correlates directly with the ability of the cancer cells to escape cell death induced by a cytotoxic T-cell-mediated immune response. Moreover, cancer cells escape from the immune response was linearly approximated (R2 equal to 0.99) with the degree by which their proteomic footprints diverged from the footprint of the targeted (native) cancer cells. From these findings, it was concluded that the design of anticancer vaccines intended to prevent cancer recurrence after primary treatment should consider the drug-specific changes in cancer cell-surface antigens. Such changes can be easily identified by cell proteomic footprinting, renewing hopes for development of efficient cellular cancer vaccines.