The association between the high-risk type-16 of the human papillomavirus (HPV-16) and a subset of headand neck squamous cell carcinomas (HNSCC) has recently been established. Given the causative role ofHPV-16 in a subset of head and neck cancers, both prophylactic and therapeutic vaccines targeted to HPV-16 are accepted as highly relevant for the prevention and treatment of HPV-HNSCC. The HPV viraloncoproteins, E6 and E7, are constitutively expressed in HPV-associated cancers; therefore, they representideal target tumor antigens for the development of antigen-specific vaccines. In preclinical studies, we havefound that a DMA vaccine comprised of a model tumor antigen (HPV-16 E7) which is physically linked to theimmunomodulatory protein calreticulin (CRT), results in potent E7-specific CD8+ T cell immune responsesand anti-tumor effects against an E7-expressing tumor model in vaccinated mice. This vaccine has alsobeen proved effective against E7-expressing murine tumors with down-regulated Major HistocompatibilityComplex (MHC) class I molecules; an important finding, given a significant proportion of advanced stageHNSCC down-regulate MHC class I molecules as a means of immune evasion. In addition, we found thatthe combination of CRT/E7 DMAvaccination and a mild chemotherapeutic agent, Epigallocatechin-3-Gallate(EGCG), a compound found in green tea, acted synergistically to enhance tumor-specific T cell immuneresponses, as well as enhance anti-tumor effects, resulting in a higher cure rate than either DNA vaccinationor EGCG alone. These findings have prompted us to investigate whether the combination of intradermaladministration of CRT/E7 DNA vaccine via gene gun and oral EGCG administration is safe and able togenerate E7-specific CD8+ T cell immune responses in patients with advanced HPV-associated head andneck cancers.
Showing the most recent 10 out of 137 publications
