Comparison of two cancer vaccines targeting tyrosinase: Plasmid DNA and recombinant alphavirus replicon particles Journal Article


Authors: Goldberg, S. M.; Bartido, S. M.; Gardner, J. P.; Guevara Patiñio, J. A.; Montgomery, S. C.; Perales, M. A.; Maughan, M. F.; Dempsey, J.; Donovan, G. P.; Olson, W. C.; Houghton, A. N.; Wolchok, J. D.
Article Title: Comparison of two cancer vaccines targeting tyrosinase: Plasmid DNA and recombinant alphavirus replicon particles
Abstract: Purpose: Immunization of mice with xenogeneic DNA encoding human tyrosinase-related proteins 1 and 2 breaks tolerance to these self-antigens and leads to tumor rejection. Viral vectors used alone or in heterologous DNA prime/viral boost combinations have shown improved responses to certain infectious diseases. The purpose of this study was to compare viral and plasmid DNA in combination vaccination strategies in the context of a tumor antigen. Experimental Design: Using tyrosinase as a prototypical differentiation antigen, we determined the optimal regimen for immunization with plasmid DNA. Then, using propagation-incompetent alphavirus vectors (virus-like replicon particles, VRP) encoding tyrosinase, we tested different combinations of priming with DNA or VRP followed by boosting with VRP. We subsequently followed antibody production, T-cell response, and tumor rejection. Results: T-cell responses to newly identified mouse tyrosinase epitopes were generated in mice immunized with plasmid DNA encoding human (xenogeneic) tyrosinase. In contrast, when VRP encoding either mouse or human tyrosinase were used as single agents, antibody and T-cell responses and a significant delay in tumor growth in vivo were observed. Similarly, a heterologous vaccine regimen using DNA prime and VRP boost showed a markedly stronger response than DNA vaccination alone. Conclusions: Alphavirus replicon particle vectors encoding the melanoma antigen tyrosinase (self or xenogeneic) induce immune responses and tumor protection when administered either alone or in the heterologous DNA prime/VRP boost approaches that are superior to the use of plasmid DNA alone. © 2005 American Association for Cancer Research.
Keywords: controlled study; survival analysis; human cell; animals; mice; in vivo study; cell line, tumor; tumor antigen; mice, inbred c57bl; immunological tolerance; immune response; amino acid sequence; cancer vaccine; cancer vaccines; vaccination; epitope; melanoma, experimental; plasmids; dna vaccine; melanoma antigen; monophenol monooxygenase; primer dna; tumor growth; dna binding; tyrosinase related protein 1; tumor rejection; virus particle; antibody production; differentiation antigen; virus vector; plasmid dna; immunization; virus dna; tyrosinase related protein 2; alpha virus; replicon; alphavirus; virus like replicon; dna, recombinant
Journal Title: Clinical Cancer Research
Volume: 11
Issue: 22
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2005-11-15
Start Page: 8114
End Page: 8121
Language: English
DOI: 10.1158/1078-0432.ccr-05-1410
PUBMED: 16299244
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 28" - "Export Date: 24 October 2012" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Jedd D Wolchok
    630 Wolchok
  2. Miguel-Angel Perales
    364 Perales
  3. Alan N Houghton
    264 Houghton
  4. Shirley M Bartido
    34 Bartido