Abstract
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)-α 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-α 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-α 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.
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Jafee, E. M. (1999) Immunotherapy of cancer. Ann. NY Acad. Sci. 886, 67–72.
Nabel, G. J. (2004) Genetic, cellular and immune approaches to disease therapy: past and future. Nat. Med. 10, 135–141.
Thomas, M. C., Greten, T. F., Pardoll, D. M., and Jaffee, E. M. (1998) Enhanced tumor protection by granulocyte-macrophage colony-stimulating factor expression at the site of an allogeneic vaccine. Hum. Gene Ther. 9, 835–843.
Dranoff G. (2003) GM-CSF-secreting melanoma vaccines. Oncogene 22, 3188–3192.
Nemunaitis, J. and Nemunaitis, J. (2003) Granulocyte-macrophage colony-stimulating factor gene-transfected autologous tumor cell vaccine: focus on non-small-cell lung cancer. Clin. Lung Cancer 5, 148–157.
Ma, W., Yu, H., Wang, Q., Jin, H., Solheim, J., and Labhasetwar, V. (2004) A novel approach for cancer immunotherapy: tumor cells with anchored superantigen SEA generate effective antitumor immunity. J. Clin. Immunol. 24, 294–301.
Liao, X., Li, Y., Bonini, C., Nair, S., Gilboa, E., Greenberg, P. D., and Yee, C. (2004) Transfection of RNA encoding tumor antigens following maturation of dendritic cells leads to prolonged presentation of antigen and the generation of high-affinity tumor-reactive cytotoxic T lymphocytes. Mol. Ther. 9, 757–764.
Hsueh, E. C., Essner, R., Foshag, L. J., Ollila, D. W., Gammon, G., O’Day, S. J., et al. (2002) Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine. J. Clin. Oncol. 20, 4549–4554.
Salem, M. L., Kadima, A. N., Zhou, Y., Nguyen, C. L., Rubinstein, M. P., Demcheva, M., et al. (2004) Paracrine release of IL-12 stimulates IFN-gamma production and dramatically enhances the antigen-specific T cell response after vaccination with a novel peptide-based cancer vaccine. J. Immunol. 172, 5159–5167.
Slingluff, C. L. Jr., Petroni, G. R., Yamshchikov, G. V., Barnd, D. L., Eastham, S., Galavotti, H., et al. (2003) Clinical and immunological results of a randomized Phase II Trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J. Clin. Oncol. 21, 4016–4026.
Maraskovsky, E., Sjolander, S., Drane, D. P., Schnurr, M., Le, T. T., Mateo, L., et al. (2004) NY-ESO-1 protein formulated in ISCOMATRIX adjuvant is a potent anticancer vaccine inducing both humoral and CD8+ t-cell-mediated immunity and protection against NY-ESO-1+ tumors. Clin. Cancer Res. 10, 2879–2890.
Sinibaldi-Vallebona, P., Rasi, G., Pierimarchi, P., Bernard, P., Guarino, E., Guadagni, F., and Garaci, E. (2004) Vaccination with a synthetic nonapeptide expressed in human tumors prevents colorectal cancer liver metastases in syngeneic rats. Int. J. Cancer 110, 70–75.
Fleischmann, C. M., Wu, T. Y., and Fleischmann, W. R. Jr. (1997) B16 melanoma cells exposed in vitro to long-term IFN-α treatment (B16α cells) as activators of host cell tumor immunity in mice. J. Interferon Cytokine Res. 17, 37–43.
Wu, T. Y. and Fleischmann, W. R. Jr. (1998) Efficacy of B16 melanoma cells exposed in vitro to long-term IFN-α treatment (B16α cells) as a tumor vaccine in mice. J. Interferon Cytokine Res. 18, 829–839.
Wu, T. Y. and Fleischmann, W. R. Jr. (2001) Murine B16 melanoma vaccination-induced tumor immunity: identification of specific immune cells and functions involved. J. Interferon Cytokine Res. 21, 1117–1127.
Wu, T. Y. and Fleischmann, W. R. Jr. Unpublished observations.
Fidler, I. J. (1973) Selection of successive tumor lines for metastasis. Nature New Biol. 242, 148–149.
Thompson, T. C., Southgate, J., Kitchener, G., and Land, H. (1989) Multi-stage carcinogenesis induced by ras and myc oncogenes in a reconstituted organ. Cell 56, 917–930.
Baley, P. A., Yoshida, K., Qian, W., Sehgal, I., and Thompson, T. C. (1995) Progression to androgen insensitivity in a novel in vitro mouse model for prostate cancer. J. Steroid Biochem. Mol. Biol. 52, 403–413.
Coveney, E., Clary, B., Philip, R., and Lyerly, K. (1996) Active immunotherapy with transiently transfected cytokine-secreting tumor cells inhibits breast cancer metastases in tumor-bearing animals. Surgery 120, 265–273.
Morecki, S., Lubina-Salomon, A., Slavin, S., and Nagler, A. (1998) Cytokine gene transduction into non-immunogeneic murine tumor cells. Cytokines Cell. Mol. Ther. 4, 87–94.
Ozer. H. L. (1966) Purine pyrophosphorylase as a selective genetic marker in a mouse lymphoma, P388, in cell culture. J. Cell Physiol. 68, 61–68.
Evinger, M., Rubinstein, M., and Pestka, S. (1981) Antiproliferative and antiviral activities of human leukocyte interferons. Arch. Biochem. Biophys. 210, 319–329.
Ortaldo, J. R., Mantovani, A., Hobbs, D., Rubinstein, M., Pestka, S., and Herberman, R. B. (1983) Effects of several species of human leukocyte interferon on cytotoxic activity of NK cells and monocytes. Int. J. Cancer 31, 285–289.
Rehberg, E., Kelder, B., Hoal, E. G., and Pestka, S. (1982) Specific molecular activities of recombinant and hybrid leukocyte interferons. J. Biol. Chem. 257, 11,497–11,502
Ortaldo, J. R., Mason, A., Rehberg, E., Kelder, B., Harvey, C., Oscheroff, P., et al. (1983) Augmentation of NK activity with recombinant and hybrid recombinant human leukocyte interferons, in The Biology of the Interferon System (DeMaeyer E. and Schellekens, H., eds.), Elsevier Science Publishers B. V., Amsterdam, Netherlands, pp. 353–358.
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Fleischmann, W.R., Wu, T.G. (2005). Development of an Interferon-Based Cancer Vaccine Protocol. In: Carr, D.J.J. (eds) Interferon Methods and Protocols. Methods in Molecular Medicine™, vol 116. Humana Press. https://doi.org/10.1385/1-59259-939-7:151
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DOI: https://doi.org/10.1385/1-59259-939-7:151
Publisher Name: Humana Press
Print ISBN: 978-1-58829-418-0
Online ISBN: 978-1-59259-939-4
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