IFN-alpha-induced murine B16 melanoma cancer vaccine cells: induction and accumulation of cell-associated IL-15.

Long-term treatment of mouse cancer cells with interferon-alpha (IFN-alpha) converts parental B16 melanoma cells to B16alpha vaccine cells. Inoculation of syngeneic mice with B16alpha vaccine cells triggers immunity to the parental B16 tumor that is mediated by host macrophages, T cells, and natural killer (NK) cells. Lymph node cells from mice inoculated with irradiated B16alpha vaccine cells, but not with irradiated parental cells, proliferate when cultured in vitro, suggesting long-term in vivo activation of lymphoid cells. Long-term IFN-alpha treatment of B16alpha vaccine cells induced both interleukin-15 (IL-15) mRNA and IL-15 protein. The bulk of the induced IL-15 remained cell associated, either cytoplasmic or associated with the cell membrane. Immunofluorescence microscopy studies showed that the cell-associated IL-15 was broadly distributed throughout the cytoplasm. These observations suggest that long-term IFN-alpha treatment may induce primarily the truncated isoform of IL-15. Vaccination with irradiated B16alpha vaccine cells may promote tumor immunity by releasing high levels of cell-associated IL-15 when spontaneously lysed or directly killed by innate immune cells. The release of accumulated cell-associated IL-15 may then trigger a host T cell response to tumor antigens and cause host development of immunity to the B16 tumor cells.

Development of an interferon-based cancer vaccine protocol: application to several types of murine cancers.

A protocol for the development of cancer vaccines is presented. The protocol is based upon the long-term in vitro treatment of cancer cells with interferon (IFN)-alpha to create cancer vaccine cells. This protocol has been used to develop cancer vaccines in mice against B16 melanoma, RM-1 prostate cancer, and P388 lymphocytic leukemia. A detailed description of the protocol is presented. Important considerations that are discussed include the method of selection of potential cancer vaccine cells that would make good models for cancer vaccines for human cancers, the effects of in vitro IFN-alpha treatment concentration on the efficacy of generated cancer vaccine cells, the differential ability of cancer cells to become efficacious cancer vaccine cells in response to IFN-alpha treatment, the determination of the effectiveness of ultraviolet-light killing of various cancer cell types for generating cancer vaccine cells, and the methods of evaluation of statistical significance of the data obtained. Potential problems also are addressed.