Abstract
Various studies have used DNA vaccination as a method of immunizing against tumors (1–12). As with any tumor vaccine, one challenge is to find a truly tumor-specific antigen (13,14). The majority of immunologically targeted tumor antigens are also expressed on a subset of normal host cells. Examples of such antigens include prostate-specific antigen, and CD20, a B cell marker. Some tumor antigens are specific for activated cells of certain types, such as carcinoembryonic antigen (CEA) or the IL-2 receptor. These are often found on embryonic or fetal cells as well as tumor cells. The carbohydrate antigens of melanomas and the immunoglobulin (Ig) idiotype of B cell lymphomas represent tumor-specific antigens (TSA). Unfortunately, TSA have not been identified in more common malignancies. Furthermore, the antigenic determinants of known TSA may differ between patients; for example, the tumor idiotype (Id) of B cell lymphoma is highly patient-specific and must be determined for each case.
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References
Watanabe, A., Raz, E., Kohsaka, H., Tighe, H., Baird, S. M., Kipps, T. J., and Carson, D. A. (1993) Induction of antibodies to a kappa V region by gene immunization. J. Immunol. 151, 2871–2876.
Raz, E., Watanabe, A., Baird, S. M., Eisenberg, R. A., Parr, T. B., Lotz, M., et al. (1993) Systemic immunological effects of cytokine genes injected into skeletal muscle. Proc. Natl. Acad. Sci. USA 90, 4523–4527.
Ciernik, I. F., Berzofsky, J. A., and Carbone, D. P. (1996) Induction of cytotoxic T lymphocytes and antitumor immunity with DNA vaccines expressing single T cell epitopes. tJ. Immunol. 156, 2369–2375.
Dilloo, D., Bacon, K., Holden, W., Zhong, W., Burdach, S., Zlotnik, A., and Brenner, M. (1996) Combined chemokine and cytokine gene transfer enhances antitumor immunity. Nat. Med. 2, 1090–1095.
Irvine, K. R., Rao, J. B., Rosenberg, S. A., and Restifo, N. P. (1996) Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. J. Immunol. 156, 238–245.
Sun, W. H., Burkholder, J. K., Sun, J., Culp, J., Turner, J., Lu, X. G., et al. (1995) In vivo cytokine gene transfer by gene gun reduces tumor growth in mice. Proc. Natl. Acad. Sci. USA 92, 2889–2893.
Hawkins, R. E., Winter, G., Hamblin, T. J., Stevenson, F. K., and Russell, S. J. (1993) A genetic approach to idiotypic vaccination. J. Immunother. 14, 273–278.
Conry, R. M., LoBuglio, A. F., Loechel, F., Moore, S. E., Sumerel, L. A., Barlow, D. L., and Curiel, D. T. (1995) A carcinoembryonic antigen polynucleotide vaccine has in vivo antitumor activity. Gene Ther. 2, 59–65.
Stevenson, F. K., Zhu, D., King, C. A., Ashworth, L. J., Kumar, S., and Hawkins, R. E. (1995) Idiotypic DNA vaccines against B-cell lymphoma. Immunol. Rev. 145, 211–228.
Stevenson, F. K., Zhu, D., King, C. A., Ashworth, L. J., Kumar, S., Thompsett, A., and Hawkins, R. E. (1995) A genetic approach to idiotypic vaccination for B cell lymphoma. Ann. NY Acad. Sci. 772, 212–226.
Hakim, I., Levy, S., and Levy, R. (1996) A nine-amino acid peptide from IL-1beta augments antitumor immune responses induced by protein and DNA vaccines. J. Immunol. 157, 5503–5511.
Syrengelas, A. D., Chen, T. T., and Levy, R. (1996) DNA immunization induces protective immunity against B-cell lymphoma. Nat. Med. 2, 1038–1041.
Golumbek, P., Levitsky, H., Jaffee, L., and Pardoll, D. M. (1993) The antitumor immune response as a problem of self-nonself discrimination: implications for immunotherapy. Immunol. Res. 12, 183–192.
MacLean, G. D. and Longenecker, B. M. (1994) New possibilities for cancer therapy with advances in cancer immunology. Can. J. Oncol. 4, 249–254.
Bogen, B., Dembic, Z., and Weiss, S. (1993) Clonal deletion of specific thymocytes by an immunoglobulin idiotype. EMBO J. 12, 357–363.
Bogen, B. (1996) Peripheral T cell tolerance as a tumor escape mechanism: deletion of CD4+ T cells specific for a monoclonal immunoglobulin idiotype secreted by a plasmacytoma. Eur. J. Immunol. 26, 2671–2679.
Bright, R. K., Shearer, M. H., and Kennedy, R. C. (1995) Nucleic acid vaccination against virally induced tumors. Ann. NY Acad. Sci. 772, 241–251.
Castrucci, M. R., Hou, S., Doherty, P. C., and Kawaoka, Y. (1994) Protection against lethal lymphocytic choriomeningitis virus (LCMV) infection by immunization of mice with an influenza virus containing an LCMV epitope recognized by cytotoxic T lymphocytes. J. Virol. 68, 3486–3490.
Davis, H. L., Schirmbeck, R., Reimann, J., and Whalen, R. G. (1995) DNA-mediated immunization in mice induces a potent MHC class I-restricted cytotoxic T lymphocyte response to the hepatitis B envelope protein. Hum. Gene Ther. 6, 1447–1456.
Haynes, J. R., Fuller, D. H., Eisenbraun, M. D., Ford, M. J., and Pertmer, T. M. (1994) Accell particle-mediated DNA immunization elicits humoral, cytotoxic, and protective immune responses. AIDS Res. Hum. Retroviruses 10(Suppl 2), S43–S45.
Hui, K. M., Sabapathy, T. K., Oei, A. A., and Chia, T. F. (1994) Generation of allo-reactive cytotoxic T lymphocytes by particle bombardment-mediated gene transfer. J. Immunol. Methods 171, 147–155.
Katsumi, A., Emi, N., Abe, A., Hasegawa, Y., Ito, M., and Saito, H. (1994) Humoral and cellular immunity to an encoded protein induced by direct DNA injection. Hum. Gene Ther. 5, 1335–1339.
Martins, L. P., Lau, L. L., Asano, M. S., and Ahmed, R. (1995) DNA vaccination against persistent viral infection. J. Virol. 69, 2574–2582.
Okuda, K., Bukawa, H., Hamajima, K., Kawamoto, S., Sekigawa, K., Yamada, Y., et al. (1995) Induction of potent humoral and cell-mediated immune responses following direct injection of DNA encoding the HIV type 1 env and rev gene products. AIDS Res. Hum. Retroviruses 11, 933–943.
Pertmer, T. M., Eisenbraun, M. D., McCabe, D., Prayaga, S. K., Fuller, D. H., and Haynes, J. R. (1995) Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine 13, 1427–1430.
Raz, E., Carson, D. A., Parker, S. E., Parr, T. B., Abai, A. M., Aichinger, G., et al. (1994) Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc. Natl. Acad. Sci. USA 91, 9519–9523.
Schirmbeck, R., Böhm, W., Ando, K., Chisari, F. V., and Reimann, J. (1995) Nucleic acid vaccination primes hepatitis B virus surface antigen-specific cytotoxic T lymphocytes in nonresponder mice. J. Virol. 69, 5929–5934.
Shiver, J. W., Perry, H. C., Davies, M. E., Freed, D. C., and Liu, M. A. (1995) Cytotoxic T lymphocyte and helper T cell responses following HIV polynucleotide vaccination. Ann. NY Acad. Sci. 772, 198–208.
Ulmer, J. B., Donnelly, J. J., Parker, S. E., Rhodes, G. H., Felgner, P. L., Dwarki, V. J., et al. (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259, 1745–1749.
Yokoyama, M., Zhang, J., and Whitton, J. L. (1995) DNA immunization confers protection against lethal lymphocytic choriomeningitis virus infection. J. Virol. 69, 2684–2688.
Zarozinski, C. C., Fynan, E. F., Selin, L. K., Robinson, H. L., and Welsh, R. M. (1995) Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein. J. Immunol. 154, 4010–4017.
Maecker, H. T., Umetsu, D. T., DeKruyff, R. H., and Levy, S. (1997) DNA vaccination with cytokine fusion constructs biases the immune response to ovalbumin. Vaccine 15, 1687–1696.
Ke, Y., Li, Y., and Kapp, J. A. (1995) Ovalbumin. injected with complete Freund’s adjuvant stimulates cytolytic responses. Eur. J. Immunol. 25, 549–553.
Hariharan, K., Braslawsky, G., Black, A., Raychaudhuri, S., and Hanna, N. (1995) The induction of cytotoxic T cells and tumor regression by soluble antigen formulation. Cancer Res. 55, 3486–3489.
Sato, Y., Roman, M., Tighe, H., Lee, D., Corr, M., Nguyen, M. D., et al. (1996) Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science 273, 352–354.
Klinman, D. M., Yi, A. K., Beaucage, S. L., Conover, J., and Krieg, A. M. (1996) CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma. Proc. Natl. Acad. Sci. USA 93, 2879–2883.
Klinman, D. M., Yamshchikov, G., and Ishigatsubo, Y. (1997) Contribution of CpG motifs to the immunogenicity of DNA vaccines. J. Immunol. 158, 3635–3639.
Reff, M. E., Carner, K., Chambers, K. S., Chinn, P. C., Leonard, J. E., Raab, R., et al. (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83, 435–445.
Torres, C. A., Iwasaki, A., Barber, B. H., and Robinson, H. L. (1997) Differential dependence on target site tissue for gene gun and intramuscular DNA immunizations. J. Immunol. 158, 4529–4532.
Condon, C., Watkins, S. C., Celluzzi, C. M., Thompson, K., and Falo, L. D., Jr. (1996) DNA-based immunization by in vivo transfection of dendritic cells. Nat. Med. 2, 1122–1128.
Tao, M. H. and Levy, R. (1993) Idiotype/granulocyte-macrophage colonystimulating factor fusion protein as a vaccine for B-cell lymphoma. Nature 362, 755–758.
Chen, T. T., Tao, M. H., and Levy, R. (1994) Idiotype-cytokine fusion proteins as cancer vaccines. Relative efficacy of IL-2, IL-4, and granulocyte-macrophage colony-stimulating factor. J. Immunol. 153, 4775–4787.
Kim, T. S., DeKruyff, R. H., Rupper, R., Maecker, H. T., Levy, S., and Umetsu, D. T. (1997) An ovalbumin-IL-12 fusion protein is more effective than ovalbumin. plus free recombinant IL-12 in inducing a T helper cell type 1-dominated immune response and inhibiting antigen-specific IgE production. J. Immunol. 158, 4137–4144.
Xiang, Z. and Ertl, H. C. (1995) Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines. Immunity 2, 129–135.
Feltquate, D. M., Heaney, S., Webster, R. G., and Robinson, H. L. (1997) Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol. 158, 2278–2284.
Beckers, W., Villa, L., Gonfloni, S., Castagnoli, L., Newton, S. M., Cesareni, G., and Ghiara, P. (1993) Increasing the immunogenicity of protein antigens through the genetic insertion of VQGEESNDK sequence of human IL-1 beta into their sequence. J. Immunol. 151, 1757–1764.
Bergman, Y. and Haimovich, J. (1977) Characterization of a carcinogen-induced murine B lymphocyte cell line of C3H/eB origin. Eur. J. Immunol. 7, 413–417.
Stuschke, M., Budach, V., Bamberg, M., and Budach, W. (1990) Methods for analysis of censored tumor growth delay data. Radiat. Res. 122, 172–180.
Maloney, D. G., Kaminski, M. S., Burowski, D., Haimovich, J., and Levy, R. (1985) Monoclonal anti-idiotype antibodies against the murine B cell lymphoma 38C13: characterization and use as probes for the biology of the tumor in vivo and in vitro. Hybridoma 4, 191–209.
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Maecker, H.T., Syrengelas, A., Levy, R. (2000). Cytokine Fusion Constructs as DNA Vaccines Against Tumors. In: Lowrie, D.B., Whalen, R.G. (eds) DNA Vaccines. Methods in Molecular Medicine™, vol 29. Humana Press. https://doi.org/10.1385/1-59259-688-6:221
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DOI: https://doi.org/10.1385/1-59259-688-6:221
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