Abstract LB-257: Immunoadjuvant ISG15 enhances human papillomavirus 16 antigen-specific cell-mediated antitumor immunity

Abstract

Abstract Adjuvants are critical components of most clinically used vaccines and act as substances to enhance adaptive immune responses to an antigen. Here we examine a new immunoadjuvant, interferon stimulated gene 15 (ISG15), for its adjuvant effects in an HPV-associated cancer immune therapy model where cell-mediated immunity is crucial for protection. ISG15 is an ubiquitin-like protein induced by type I interferon and associated with antiviral activity. Recent studies of ISG15 have re-established that ISG15 is also a secreted molecule with cytokine-like properties. However, the potential ability of ISG15 to influence the Th1 and CD8 T cell immune responses and act a vaccine adjuvant, has not been well defined. To this end, we developed a highly optimized DNA-vector encoding the ISG15 protein and evaluated its immunogenicity to increase the cellular immune responses in combination with a DNA consensus-based fusion HPV16 E6/E7 construct. We demonstrate that ISG15 can enhance Ag-specific Th1 memory responses to HPV16 E6/E7 antigen by IFN-γ ELISpot analysis. Moreover, ISG15 elicited strong HPV16 Ag-specific polyfunctional CD8+ T cells that secrete both anti-viral IFN-γ and/or TNF-α cytokines. Vaccination conferred remarkable 100% protection against challenge with HPV E6 and E7-expressing tumors. Overall, these findings lay the groundwork of ISG15 as a new immunoadjuvant candidate in the context of cancer immunotherapy. Citation Format: Daniel Villarreal, Megan C. Wise, Jian Yang, David B. Weiner. Immunoadjuvant ISG15 enhances human papillomavirus 16 antigen-specific cell-mediated antitumor immunity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-257. doi:10.1158/1538-7445.AM2014-LB-257