TriVax-HPV: An improved peptide-based therapeutic vaccination strategy against human papillomavirus-induced cancers

Abstract

Background Therapeutic vaccines for cancer are an attractive alternative to conventional therapies, since the later result in serious adverse eVects and in most cases are not eVective against advanced disease. Human papillomavirus (HPV) is responsible for several malignancies such as cervical carcinoma. Vaccines targeting oncogenic viral proteins like HPV16-E6 and HPV16-E7 are ideal candidates to elicit strong immune responses without generating autoimmunity because: (1) these products are not expressed in normal cells and (2) their expression is required to maintain the malignant phenotype. Our group has developed peptide vaccination strategy called TriVax, which is eVective in generating vast numbers of antigen-speciWc T cells in mice capable of persisting for long time periods. Materials and methods We have used two HPV-induced mouse cancer models (TC-1 and C3.43) to evaluate the immunogenicity and therapeutic eYcacy of TriVax prepared with the immunodominant CD8 T-cell epitope HPV16-E749-57, mixed with poly-IC adjuvant and costimulatory anti-CD40 antibodies. Results TriVax using HPV16-E749-57 induced large and persistent T-cell responses that were therapeutically eVective against established HPV16-E7 expressing tumors. In most cases, TriVax was successful in attaining complete rejections of 6-11-day established tumors. In addition, TriVax induced long-Term immunological memory, which prevented tumor recurrences. The anti-Tumor eVects of TriVax were independent of NK and CD4 T cells and, surprisingly, did not rely to a great extent on type-I or type-II interferon. Conclusions These Wndings indicate that the TriVax strategy is an appealing immunotherapeutic approach for the treatment of established viral-induced tumors. We believe that these studies may help to launch more eVective and less invasive therapeutic vaccines for HPV-mediated malignancies. © Springer-Verlag 2012.