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DNA Vaccine Strategies for the Treatment of Cancer

  • Chapter
DNA Vaccination/Genetic Vaccination

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 226))

Abstract

A wide variety of immunotherapeutic strategies for the treatment of cancers is currently under investigation in both animal models and in clinical human trials (reviewed in Dranoff and Mulligan 1995). These include in vitro expansion and adoptive transfer of tumor-specific cytotoxic T cells in the presence or absence of recombinant cytokines (Rosenberg et al. 1985, 1986, 1988, 1989, 1991, 1993; Teng et al. 1991), tumor antigen-based vaccines (Cheever et al. 1986; Bright et al. 1994a; Conry et al. 1994; Stevenson et al. 1995), and tumor-reactive monoclonal antibodies conjugated to toxins (Trail et al. 1993; Vivetta et al. 1993). One of the most recent and innovative strategies has been based on the concept of genetic immunization. It is now well established that vaccination with plasmid DNA encoding a specific gene can elicit strong, long-lived protective immune responses to a variety of infectious agents (reviewed in Ulmer et al. 1996; Whalen 1996) as well as certain tumors (Conry et al. 1994; Nabel et al. 1994b; Stevenson et al. 1995; Bright et al. 1996; Corr et al. 1996; Schirmbeck et al. 1996). DNA vaccines directed at eliciting an immune response toward tumors appear to offer promise for both the prophylactic and therapeutic treatment of cancer.

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References

  • Anderson JL, Martin RG, Chang C, Mora PT and Livingston DM (1977) Nuclear preparations of SV40 transformed cells contain tumor specific transplantation antigen activity. Virology 76:420–425

    Article  PubMed  CAS  Google Scholar 

  • Bright RK, Beames B, Shearer MH and Kennedy RC (1996) Protection against a lethal tumor challenge with simian virus 40 transformed cells by the direct injection of DNA encoding SV40 large tumor antigen. Cancer Res 56:1126–1130

    PubMed  CAS  Google Scholar 

  • Bright RK, Shearer MH and Kennedy RC (1994a) Immunization of BALB/c mice with recombinant simian virus 40 large tumor antigen induces antibody-dependent cell-mediated cytotoxicity against simian virus 40-transformed cells. J Immunol 153:2064–2071

    PubMed  CAS  Google Scholar 

  • Bright RK, Shearer MH and Kennedy RC (1994b) SV40 large tumor antigen associated synthetic peptides define native antigenic determinants and induce protective tumor immunity in mice. Mol Immunol 29:989–999

    Google Scholar 

  • Browning MJ and Bodmer WF (1992) MHC antigens and cancer: Implications for T-cell surveillance. Curr Opinion Immunol 4:613–618

    Article  CAS  Google Scholar 

  • Carrel S and Rimoldi D (1993) Melanoma associated antigens. Eur J Cancer 29A:1903–1907

    Article  PubMed  CAS  Google Scholar 

  • Chang C, Martin RG, Livingston DM, Luborsky SW, Hu CP and Mora PT (1979) Relationship between T-antigen and tumor-specific transplantation antigen in simian virus 40 transformed cells. J Virol 29:69–75

    PubMed  CAS  Google Scholar 

  • Cheever MA, Britzmann-Thompson D, Klarnet JP and Greenberg PI (1986) Antigen-driven long term- cultured T cells proliferate in vivo, distribute widely, mediate specific tumor therapy, and persist longterm as functional memory T cells. J Exp Med 163:1100–1112

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Ashe S, Brady WA, Hellstrom I, Hellstrom KE, Ledbetter JA, McGowan P and Linsley PS (1992) Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 71:1093–1102

    Article  PubMed  CAS  Google Scholar 

  • Ciernik IF, Berzofsky JA and Carbone DP (1996) Induction of cytotoxic T lymphocytes and antitumor immunity with DNA vaccines expressing single T cell epitopes. J Immunol 156:2369–2375

    PubMed  CAS  Google Scholar 

  • Cohen J (1993) Cancer vaccines get a shot in the arm. Science 262:841–843

    Article  PubMed  CAS  Google Scholar 

  • Conry RM, LoBuglio AF, Kantor J, Schlom J, Loechel F, Moore SE, Sumerel LA, Barlow DL, S. A and Curiel DT (1994) Immune response to a carcinoembryonic antigen polynucleotide vaccine. Cancer Res 54:1164–1168

    PubMed  CAS  Google Scholar 

  • Corr M, Lee DJ, Carson DA and Tighe H (1996) Gene vaccination with naked plasmid DNA: mechanism of CTL priming. J Exp Med 184:1555–1560

    Article  PubMed  CAS  Google Scholar 

  • Cristiano RJ, Smith LC, Brinkley BR and Woo SL (1993a) Hepatic gene therapy: Efficient gene delivery and expression in primary hepatocytes utilizing a conjugated adenovirus-DNA complex. Proc Natl Acad Sci USA 90:11548–11552

    Article  PubMed  CAS  Google Scholar 

  • Cristiano RJ, Smith LC and Woo SLC (1993b) Hepatic gene therapy: Adenovirus enhancement of receptor-mediated gene delivery and expression in primary hepatocytes. Proc Natl Acad Sci USA 90:2122–2126

    Article  PubMed  CAS  Google Scholar 

  • Davis HL, Michel ML and Whalen RG (1995) Use of plasmid DNA for direct gene transfer and immunization. Ann New York Acad Sci 772:21–29

    Article  CAS  Google Scholar 

  • Dranoff G and Mulligan RC (1995) Gene transfer as cancer therapy. Adv Immunol 58:417–454

    Article  PubMed  CAS  Google Scholar 

  • Eisen HN, Sakato N and Hall SJ (1975) Myeloma proteins as tumor-specific antigens. Transplant Proc 7:209–214

    PubMed  CAS  Google Scholar 

  • Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B and Frost P (1990) Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60:397–403

    Article  PubMed  CAS  Google Scholar 

  • Foecking MK and Hofstetter H (1986) Powerful and versatile enhancer-promoter unit for mammalian expression vectors. Gene 45:101–105

    Article  PubMed  CAS  Google Scholar 

  • Foley EJ (1953) Antigenic properties of methylcholanthrene-induced tumor in mice of the strain of origin. Cancer Res 13:835–837

    PubMed  CAS  Google Scholar 

  • Gansbacher B, Bannerji R, Daniels B, Zier K, Cronin K and Gilboa E (1990a) Retroviral vector- mediated g-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 50:7820–7825

    PubMed  CAS  Google Scholar 

  • Gansbacher B, Zier K, Daniels B, Kronin K, Bannerji R and Gilboa E (1990b) Interleukin-2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 172:1217–1224

    Article  PubMed  CAS  Google Scholar 

  • Gooding LR (1977) Specificities of killing by cytotoxic lymphocytes generated in vivo and in vitro to syngeneic SV40 transformed cells. J Immunol 118:920–927

    PubMed  CAS  Google Scholar 

  • Gross L (1943) Intradermal immunization of C3H mice against a sarcoma that originated in an animal of the same line. Cancer Res 3:326–333

    Google Scholar 

  • Hassett DE and Whitton JL (1996) DNA immunization. Trends in Microbiology 4:307–312

    Article  PubMed  CAS  Google Scholar 

  • Hawkins RE, Winter G, Hamblin TJ, Stevenson FK and Russell SJ (1993) A genetic approach to idiotypic vaccination. J Immunother 14:273–278

    Article  CAS  Google Scholar 

  • Hawkins RE, Zhu D, Ovecka M, Winter G, Hamblin TJ, Long A and Stevenson FK (1994) Idiotypic vaccination against human B-cell lymphoma. Rescue of variable region gene sequences from biopsy material for assembly as single-chain antibodies Fv personal vaccines. Blood 83:3279–3288

    PubMed  CAS  Google Scholar 

  • Hui K, Grosveld F and Festenstein (1984) Rejection of transplantable leukemia cells following MHC DNA-mediated cell transformation. Nature 311:750–752

    Article  PubMed  CAS  Google Scholar 

  • Irvine KR, Rao JB, Rosenberg SA and Restifo NP (1996) Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. J Immunol 156:238–245

    PubMed  CAS  Google Scholar 

  • Kawakami Y, Robbins PF, Wang RF, Rosenberg SA (1996) Identification of tumor-regression antigens in melanoma. In: DeVita VT, Heilman S, Rosenberg SA (eds) Advances in oncology, Lippincott- Raven, Philadelphia, pp 3–21

    Google Scholar 

  • Kennedy RC, Dreesman GR, Butel JS and Lanford RE (1985) Suppression of in vivo tumor formation induced by simian virus 40-transformed cells in mice receiving anti-idiotypic antibodies. J Exp Med 161:1432–1449

    Article  PubMed  CAS  Google Scholar 

  • Kennedy RC, Zhou E-M, Lanford RE, Chanh TC and Bona CA (1987) Possible role of anti-idiotypic antibodies in the induction of tumor immunity. J Clin Invest 80:1217–1224

    Article  PubMed  CAS  Google Scholar 

  • Knowles BB, Koncar M, Pfizenmaier, K., Solter D, Aden DP and Trinchieri G (1979) Genetic control of the cytotoxic T cell response to SV40 tumor associated specific antigen. J Immunol 122:1798–1806

    PubMed  CAS  Google Scholar 

  • Krieg P, Amtmann E, Jonas D, Fisher H, Zang K and Sauer G (1981) Episomal simian virus 40 genomes in human brain tumors. Proc Natl Acad Sci USA 10

    Google Scholar 

  • Mernaugh RL, Shearer MH, Bright RK, Lanford RE and Kennedy RC (1992) Idiotypic network components are involved in the murine immune response to simian virus 40 large tumor antigen. Cancer Immunol Immunother. 35:113–118

    Article  PubMed  CAS  Google Scholar 

  • Moller P and Hammerling G (1992) The role of surface HLA-A, B, C molecules in tumor immunity. Cancer Surg 13:101–128

    CAS  Google Scholar 

  • Mule JJ, Shu S, Schwarz SL and Rosenberg SA (1984) Adoptive immunotherapy of established pulmonary métastasés with LAK cell and recombinant interleukin-2. Science 225:1487–89

    Article  PubMed  CAS  Google Scholar 

  • Nabel EG, Yang Z-Y, Muller D, Chang AE, Gao X, Huang L, Cho KJ and Nabel GJ (1994a) Safety and toxicity of catheter gene delivery to the pulmonary vasculature in a patient with metastatic melanoma. Hum Gene Ther 5:1089–1094

    Article  PubMed  CAS  Google Scholar 

  • Nabel GJ, Nabel EG, Yang Z, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D and Chang AE (1994b) Molecular genetic interventions for cancer. Cold Spring Harbor Symposia on Quantitative Biology 59:699–707

    PubMed  CAS  Google Scholar 

  • Nabel GJ, Nabel EG, Yang Z-Y, Fox BA, Plautz GE, Gao X, Huang L, Shu S and Chang AE (1993) Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc Natl Acad Sci USA 90:11307–11311

    Article  PubMed  CAS  Google Scholar 

  • Pass HI, Kennedy RC and Carbone M (1996) Evidence for and implications of SV40-like sequences in human mesotheliomas. In: Important advances in oncology 1996. Devita VT, Heilman S, Rosenberg SA, eds. Lippincott-Raven, Philadelphia pp 89–108

    Google Scholar 

  • Plautz GE, Yang ZY, Gao X, Huang L and Nabel GJ (1993) Immunotherapy of malignancy by in vivo gene transfer into tumors. Proc Natl Acad Sci USA 90:4645

    Article  PubMed  CAS  Google Scholar 

  • Prehn RT and Main JM (1957) Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst 18:769–778

    PubMed  CAS  Google Scholar 

  • Raz E, Carson DA, Parker SE, Parr TB, Abai AM, Aichinger G, Gromkowski SH, Singh M, Lew D, Yankauckas MA, Baird SM and Rhodes GH (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

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg SA (1991) Immunotherapy and gene therapy of cancer. Cancer Res (Suppl) 51:5074s–5079s

    CAS  Google Scholar 

  • Rosenberg SA, Anderson WF, Asher AL, Blaese MR, Ettinghausen SE, Hwu P, Kasid A, Mule JJ, Parkinson DR, Schwartzentruber DJ, Topalian SL, Weber JS, Yannelli JR, Yang JC and Linehan WM (1992a) Immunization of cancer patients using autologous cancer cells modified by insertion of the gene for interleukin-2. Human Gene Therapy 3:75–90

    Article  Google Scholar 

  • Rosenberg SA, Anderson WF, Asher AL, Blaese MR, Ettinghausen SE, Hwu P, Kasid A, Mule JJ, Parkinson DR, Schwartzentruber DJ, Topalian SL, Weber JS, Yannelli JR, Yang JC and Linehan WM (1992b) Immunization of cancer patients using autologous cancer cells modified by insertion of the gene for tumor necrosis factor. Human Gene Therapy 3:57–73

    Article  Google Scholar 

  • Rosenberg SA, Lotze MA, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp CA, Simpson C and Reichert CM (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients wiht metastatic cancer. N Eng J Med 313:1485–1492

    Article  CAS  Google Scholar 

  • Rosenberg SA, Lotze MT, Yang JC, Aebersold PA, Linehan WM, Seipp CA and White DE (1989) Experience with the use of high-dose interleukin-2 in the treatment of 652 patients with cancer. Ann Surg 210:474–485

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg SA, Lotze MT, Yang JC, Topalian SL, Chang AE, Schwartzentruber DJ, Aebersold P, Leitman S, Linehan WM and Seipp CAea (1993) Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst 85:622–632

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, Simpson C, Carter C, Bock S, Schwartzentruber D, Wei JP and White DE (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. N Engl J Med 319:1676–1680

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg SA, Spiess P and Lafreniere R (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233:1318–1321

    Article  PubMed  CAS  Google Scholar 

  • Roth C, Rochlitz C and Kourilsky P (1994) Immune response against tumors. Adv Immunol 57:281–351

    Article  PubMed  CAS  Google Scholar 

  • Samson JH, Archer GE, Ashley DM, Fuchs HE, Hale LP, Dranoff G and Bigner DD (1996) Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the “immunologically privileged” central nervous system. Proc Natl Acad Sci USA 93:10399–10404

    Article  Google Scholar 

  • Schirmbeck R, Bohm W and Reimann J (1996) DNA vaccination primes MHC class I-restricted, simian virus 40 large tumor antigen-specific CTL in H-2d mice that reject syngeneic tumors. J Immunol 157:3550–3558

    PubMed  CAS  Google Scholar 

  • Schirmbeck R, Zerrahn J, Kuhrober A, Kury E, Deppert W and Reimann J (1992) Immunization with soluble simian virus 40 large T antigen induces a specific response of CD3+ C4–CD8+ cytotoxic T lymphocytes in mice. Eur J Immunol 22:759–766

    Article  PubMed  CAS  Google Scholar 

  • Schwartz RH (1992) Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71:1065–1068

    Article  PubMed  CAS  Google Scholar 

  • Shearer MH, Bright RK and Kennedy RC (1993) Comparison of the humoral immune responses and tumor immunity in mice immunized with recombinant SV40 large tumor antigen and a monoclonal anti-idiotype. Cancer Res 53:5734–5739

    PubMed  CAS  Google Scholar 

  • Stevenson FK, Zhu D, King CA, Ashworth LJ, Kumar S and Hawkins RE (1995) Idiotypic DNA vaccines against B-cell lymphoma. Immunol Rev 145:211–228

    Article  PubMed  CAS  Google Scholar 

  • Tanaka K, Isselbacher KJ, Khoury G and Jay G (1985) Reversal of oncogenesis by the expression of H-2 K antigen following H-2 gene transfection. Science 228:26–30

    Article  PubMed  CAS  Google Scholar 

  • Teng MN, Park BH, Koeppen HK, Tracey KJ, Fendly BM and Schreiber H (1991) Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T-cell immunity. Proc Natl Acad Sci USA 88:3535–3539

    Article  PubMed  CAS  Google Scholar 

  • Tepper RI, Pattengale PK and Leder P (1989) Murine interleukin-4 displays potent antitumor activity in vivo. Cell 57:503–512

    Article  PubMed  CAS  Google Scholar 

  • Tevethia SS, Flyer DC and Tjian R (1980) Biology of simian virus 40 (SV40) transplantation antigen (TrAg). VI. Mechanism of induction of SV40 transplantation immunity in mice by purified SV40 T antigen (D2 protein). Virology 107:13–23

    Article  PubMed  CAS  Google Scholar 

  • Townsend SE and Allison JP (1993) Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 259: 368–270

    Article  PubMed  CAS  Google Scholar 

  • Trail P, Wilner D, Lasch SJ, Henderson AJ, Hofstead S, Casazza AM, Firestone RA, Hellstrom I and Hellstrom KE (1993) Cure of xenografted human carcinomas by BR96-doxorubucin immunocon- jugates. Science 261:212–215

    Article  PubMed  CAS  Google Scholar 

  • Ulmer JB, Donnelly JJ and Liu MA (1996) DNA vaccines promising: a new approach to inducing protective immunity. ASM news 62:476–479

    Google Scholar 

  • Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Feigner PL, Dwarki VJ, Gromkowski SH, Deck RR, DeWitt CM, Friedman A, Hawe LA, Leander KR, Martinez D, Perry HC, Shiever JW, Montgomery DL and Liu MA (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259:1745–1749

    Article  PubMed  CAS  Google Scholar 

  • Vile RG and Hart IR (1993) In vitro and vivo targeting of gene expression to melanoma cells. Cancer Res 53:962–967

    PubMed  CAS  Google Scholar 

  • Vivetta ES, Thorpe PE and Uhr JW (1993) Immunotoxins: magic bullets or misguided missiles. Immunol Today 14:252–259

    Article  Google Scholar 

  • Wagner E, Plank C, Zatloukal K, Cotten M and Birnsteiel ML (1992a) Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes: Toward a synthetic virus-like gene-transfer vehicle. Proc Natl Acad Sci USA 89:7934–7938

    Article  PubMed  CAS  Google Scholar 

  • Wagner E, Zatloukal K, Cotten M, Kirlappos H, Mechtler K, Curiel DT and Birnsteil ML (1992b) Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. Proc Natl Acad Sci USA 89:6099–6103

    Article  PubMed  CAS  Google Scholar 

  • Wallich R, Bulbuc N, Hammerling G, Katzav S, Segal S and Feldman M (1985) Abrogation of metastatic properties of tumor cells by de novo expression of H-2 K antigen following H-2 gene transfection. Nature 315:301–305

    Article  PubMed  CAS  Google Scholar 

  • Wang B, Merva M, Dang K, Ugen KE, Williams WV and Weiner DB (1995) Immunization by direct DNA inoculation induces rejection of tumor cell challenge. Human Gene Ther 6:407–418

    Article  CAS  Google Scholar 

  • Watanabe Y, Kuribayashi K, Miyatake S, Nishihara K, Nakayama E, Taniyama R and Sakata T (1989) Exogenous expression of mouse interferon g cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity. Proc Natl Acad Sci USA 86:9456–9460

    Article  PubMed  CAS  Google Scholar 

  • Whalen RG (1996) DNA vaccines for emerging infectious diseases: what if? Emerg Inf Dis 2:168–175

    Article  CAS  Google Scholar 

  • Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A and Feigner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468

    Article  PubMed  CAS  Google Scholar 

  • Xiang Z and Ertl HC (1995) Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines. Immunity 2:129–135

    Article  PubMed  CAS  Google Scholar 

  • Zhu N, Liggitt D, Liu Y and Debs R (1993) Systemic gene expression after intravenous DNA delivery into adult mice. Science 261:209–211

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman W and Thompson J (1990) Recent developments concerning the carcinoembryonic gene family and their clinical applications. Tumor Biol 11:1–4

    Article  Google Scholar 

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Benton, P.A., Kennedy, R.C. (1998). DNA Vaccine Strategies for the Treatment of Cancer. In: Koprowski, H., Weiner, D.B. (eds) DNA Vaccination/Genetic Vaccination. Current Topics in Microbiology and Immunology, vol 226. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80475-5_1

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