High-dose chemotherapy augments the efficacy of recombinant adenovirus vaccines and improves the therapeutic outcome.

Abstract

We have investigated the therapeutic potential of a prototypic melanoma vaccine based on recombinant adenovirus expressing human dopachrome tautomerase in the B16F10 murine melanoma model. We found that in the presence of a tumor, the magnitude of T-cell immunity evoked by the vaccine was significantly reduced. This impairment was compounded by defects in cytokine production and degranulation within the tumor-infiltrating lymphocytes (TILs). We showed that the combination of vaccination with high-dose cyclophosphamide was able to skew the response toward the target antigen and enhanced both the quantity and quality of antigen-specific CD8+ and CD4+ T-cell responses in tumor-bearing mice, which resulted in the inhibition of tumor growth. Furthermore, when tumor-specific antigens were targeted by the vaccine, the combination therapy could actually produce tumor regression, which appeared to result from the high frequency of antigen-specific T cells. These data show that recombinant adenovirus vaccines are compatible with conventional high-dose chemotherapy and that the combined treatment results in improved therapeutic outcomes relative to either agent individually.

• Authors: N Grinshtein, M Ventresca, R Margl, D Bernard, T-C Yang, J B Millar, J Hummel, F Beermann, Y Wan, J L Bramson
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 16 Issue 4 Pg. 338-50 (Apr 2009) ISSN: 1476-5500 [Electronic] England
• PMID: 18989352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Cancer Vaccines
• Membrane Glycoproteins
• Vaccines, DNA
• Cyclophosphamide
• Oxidoreductases
• TYRP1 protein, human
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Adenoviridae (genetics)
• Animals
• Antineoplastic Agents, Alkylating (administration & dosage)
• Cancer Vaccines (therapeutic use)
• Cell Line, Tumor
• Combined Modality Therapy
• Cyclophosphamide (administration & dosage)
• Female
• Genetic Vectors
• Humans
• Immunity, Cellular (drug effects)
• Intramolecular Oxidoreductases (biosynthesis, genetics, immunology)
• Melanoma, Experimental (immunology, therapy)
• Membrane Glycoproteins (biosynthesis, genetics, immunology)
• Mice
• Neoplasm Transplantation
• Oxidoreductases (biosynthesis, genetics, immunology)
• Treatment Outcome
• Vaccines, DNA (therapeutic use)