DNA vaccine encoding heat shock protein 60 co-linked to HPV16 E6 and E7 tumor antigens generates more potent immunotherapeutic effects than respective E6 or E7 tumor antigens

Abstract

Objective.: Vaccination based on tumor antigen is an attractive strategy for cancer prevention and therapy. Cervical cancer is highly associated with human papillomavirus, especially type 16. We developed DNA vaccines encoding heat shock protein 60 (HSP60) linked to HPV16 E6 or E7 to test if HSP60 chimeric DNA vaccines may generate strong E6 and/or E7-specific immune response and anti-tumor effects in vaccinated mice. Methods.: In vivo antitumor effects such as preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays such as intracellular cytokine stainings, ELISA for Ab responses, and direct and cross-priming effects, were also performed. Results.: HSP60 chimeric DNA vaccines generated strong E6- or E7-specific immune responses and anti-tumor effects in vaccinated mice via direct and cross-priming effects. HSP60 was also linked with both E6 and E7 antigens and the HSP60/E6/E7 chimeric DNA vaccine generated more potent immunotherapeutic effects on E6- and E7-expressing tumors than HSP60/E6 or HSP60/E7 chimeric DNA vaccine alone. Conclusion.: Utilization of both E6 and E7 tumor antigens can advance the therapy of tumors associated with HPV-infections. The DNA vaccine encoding heat shock protein 60 co-linked to HPV16 E6 and E7 tumor antigens can generate more potent immunotherapeutic effects than E6 or E7 tumor antigens alone. ? 2007 Elsevier Inc. All rights reserved.