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Comparison of two cancer vaccines targeting tyrosinase: plasmid DNA and recombinant alphavirus replicon particles.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2005 Nov 15; Vol. 11 (22), pp. 8114-21. - Publication Year :
- 2005
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Alphavirus genetics
Amino Acid Sequence
Animals
Cancer Vaccines genetics
Cell Line, Tumor
DNA, Recombinant administration & dosage
DNA, Recombinant genetics
DNA, Recombinant immunology
Humans
Immunization methods
Melanoma, Experimental pathology
Melanoma, Experimental prevention & control
Mice
Mice, Inbred C57BL
Monophenol Monooxygenase genetics
Plasmids administration & dosage
Plasmids genetics
Plasmids immunology
Replicon genetics
Survival Analysis
Cancer Vaccines immunology
Melanoma, Experimental immunology
Monophenol Monooxygenase immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 11
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 16299244
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-05-1410