A A Clinical Odyssey: Cancer Stem Cells as the Antigen Source for Autologous Cancer Vaccines

Abstract

For 30 years we have been evaluating therapeutic cancer vaccines that present  tumor antigens from short-term cultures of self-renewing autologous cancer cells derived from surgically resected tumor. The cells derived from these cultures establish tumors in athymic mice, self-renew ex vivoin culture, and a high percentage of cells express phenotypic markers associated with stem cells of the tissue of origin; therefore these are considered to be tumor initiating cells that include cancer stem cells and their early progenitor cells. Vaccines consisting of irradiated autologous tumor cells from such short-term cell cultures were tested in patients with melanoma, renal cell cancer, and sarcomas.  Vaccines consisting of autologous dendritic cells loaded with antigens from such cell cultures have been tested in patients with melanoma, kidney, and hepatocellular cancer. Historical comparisons and randomized trials showed that survival outcomes were better for patients injected subcutaneously with dendritic cells that had been co-cultured with irradiated tumor cells for antigen presentation compared to injections of the irradiated cells. Recent improvements in manufacturing include using serum-free medium, limiting the duration of cell culture, and culturing dendritic cells with a lysate of irradiated tumor cells rather than intact irradiated tumor cells.  Trials are ongoing in patients with newly diagnosed advanced ovary cancer (stage 3 or 4), glioblastoma, and metastatic melanoma.