Heterologous Prime-Boost Vaccination in Tumor Immunotherapy

  • Michael J. Palmowski
  • Caroline Smith
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Most of the vaccine strategies under development use multiple immunizations with the same agent such as a viral vector encoding a tumor antigen. More recently, the concept of heterologous prime-boost immunization has been tested in animal models. This strategy involves the sequential administration of different delivery vectors encoding the same recombinant antigen (1). Initially demonstrated in animal studies of infectious diseases, such as malaria (1,2) and AIDS (3), prime-boost technology is now being developed for use in tumor patients (4).


Delivery Vector Recombinant Antigen Semliki Forest Virus Recombinant Vaccinia Virus Immunotherapy Strategy 
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  1. 1.
    Li S, Rodrigues M, Rodriguez D, et al. Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. Proc Natl Acad Sci USA 1993; 90:5214–5218.PubMedCrossRefGoogle Scholar
  2. 2.
    Schneider J, Gilbert SC, Blanchard TJ, et al. Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nat Med 1998; 4:397–402.PubMedCrossRefGoogle Scholar
  3. 3.
    Amara RR, Villinger F, Altman JD, et al. Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 2001; 292:69–74.PubMedCrossRefGoogle Scholar
  4. 4.
    Palmowski MJ, Choi EM, Hermans IF, et al. Competition between CTL narrows the immune response induced by prime-boost vaccination protocols. J Immunol 2002; 168:4391–4398.PubMedGoogle Scholar
  5. 5.
    Marshall JL, Hoyer RJ, Toomey MA, et al. Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses. J Clin Oncol 2000; 18:3964–3973.PubMedGoogle Scholar
  6. 6.
    Oertli D, Marti WR, Zajac P, et al. Rapid induction of specific cytotoxic T lymphocytes against melanoma-associated antigens by a recombinant vaccinia virus vector expressing multiple immunodominant epitopes and costimulatory molecules in vivo. Hum Gene Ther 2002; 13:569–575.PubMedCrossRefGoogle Scholar
  7. 7.
    Flynn KJ, Belz GT, Altman JD, Ahmed R, Woodland DL, Doherty PC. Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. Immunity 1998; 8:683–691.PubMedCrossRefGoogle Scholar
  8. 8.
    Flynn KJ, Riberdy JM, Christensen JP, Altman JD, Doherty PC. In vivo proliferation of naive and memory influenza-specific CD8(+) T cells. Proc Natl Acad Sci USA 1999; 96:8597–8602.PubMedCrossRefGoogle Scholar
  9. 9.
    Crowe JE, Jr. Influence of maternal antibodies on neonatal immunization against respiratory viruses. Clin Infect Dis 2001; 33:1720–1727.PubMedCrossRefGoogle Scholar
  10. 10.
    McAneny D, Ryan CA, Beazley RM, Kaufman HL. Results of a phase I trial of a recombinant vaccinia virus that expresses carcinoembryonic antigen in patients with advanced colorectal cancer. Ann Surg Onirol 1996. 1.495–500CrossRefGoogle Scholar
  11. 11.
    Ramshaw IA, Ramsay AJ. The prime-boost strategy: exciting prospects for improved vaccination. Immunol Today 2000; 21:163–165.PubMedCrossRefGoogle Scholar
  12. 12.
    Mateo L, Gardner J, Chen Q, et al. An HLA-A2 polyepitope vaccine for melanoma immunotherapy. J Immunol 1999; 163:4058–4063.PubMedGoogle Scholar
  13. 13.
    Kedl RM, Rees WA, Hildeman DA, et al. T cells compete for access to antigen-bearing antigenpresenting cells. J Exp Med 2000; 192:1105–1113.PubMedCrossRefGoogle Scholar
  14. 14.
    Yewdell JW, Bennink JR. Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annu Rev Immunol 1999; 17:51–88.PubMedCrossRefGoogle Scholar
  15. 15.
    Sandberg JK, Grufman P, Wolpert EZ, Franksson L, Chambers BJ, Karre K. Superdominance among immunodominant H-2Kb-restricted epitopes and reversal by dendritic cell-mediated antigen delivery. J Immunol 1998; 160:3163–3169.PubMedGoogle Scholar
  16. 16.
    Greiner JW, Zeytin H, Anver MR, Schlom J. Vaccine-based therapy directed against carcinoembryonic antigen demonstrates antitumor activity on spontaneous intestinal tumors in the absence of autoimmunitv. Cancer Res 2002; 62:6944–6951.PubMedGoogle Scholar
  17. 17.
    Pasquini S, Peralta S, Missiaglia E, Carta L, Lemoine NR. Prime-boost vaccines encoding an intracellular idiotype/GM-CSF fusion protein induce protective cell-mediated immunity in murine pre-B cell leukemia. Gene Ther 2002; 9:503–510.PubMedCrossRefGoogle Scholar
  18. 18.
    Meng WS, Butterfield LH, Ribas A, Dissette VB, Heller JB, Miranda GA, Glaspy JA, McBride WH, Economou JS. alpha-Fetoprotein-specific tumor immunity induced by plasmid prime-adenovirus boost genetic vaccination. Cancer Res 2001; 61:8782–8786.PubMedGoogle Scholar
  19. 19.
    Tuettenberg A, Jonuleit H, Tuting T, Bruck J, Knop J, Enk AH. Priming of T cells with Ad-transduced DC followed by expansion with peptide-pulsed DC significantly enhances the induction of tumorspecific CD8(+) T cells: implications for an efficient vaccination strategy. Gene Ther 2003; 10:243–250.PubMedCrossRefGoogle Scholar

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© Humana Press Inc. 2004

Authors and Affiliations

  • Michael J. Palmowski
  • Caroline Smith

There are no affiliations available

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