Cellular immune response in mucosal sites induced by a DNA vaccine against HPV-Induced tumors

Abstract

Persistent infection with oncogenic HPV are associated with various cancers including cervical cancer, the second leading cause of cancer death in women. The viral oncoproteins E6 and E7 are expressed by all tumor cells, representing ideal targets for the development of immunotherapeutic strategies. In mice, therapeutic vaccination approaches were able to confer protection against intravenous or subcutaneous implantation of cells expressing HPV-16 E6 and E7 (TC-1 cells). However, no vaccine strategy was satisfactory to promote their licensing for human use, indicating that the TC-1 animal model tested in these conditions is not necessarily predictive of the clinical outcome of therapeutic vaccines. In this context, the group led by Prof. Eric Tartour (Paris Descartes) has developed a sublingual engraftment of TC-1 cells, simulating tumors of the head and neck cancers, which allows the evaluation of mucosal and cellular immune response induced by a vaccine. In our laboratory, we developed a DNA vaccine strategy against tumors induced by HPV that was capable of conferring superior protection in the subcutaneous model of TC-1 cells than other vaccines described in the literature. The present project will provide the evaluation of our vaccine in the mucosal tumors animal model and in tolerogenic animals, corresponding to more restrictive models that may correlate better with protective response in patients. (AU)