mRNA-HPV Therapeutic Vaccine Encoding E6 and E7 Improves Therapeutic Potential in HPV-mediated Cancer

Abstract The viral E6 and E7 oncoproteins of human papillomavirus (HPV) are strongly associated with cervical cancer. We developed and assessed the efficacy of an mRNA-HPV therapeutic vaccine (mHTV), containing the E6 and E7 proteins, in C57BL/J mice. mHTV generated robust T cell-mediated immune responses and induced short-lived effector and E7 tetramer-specific T cells. mHTV immunization significantly suppressed tumor growth in mice implanted with TC-1 tumor cells and improved overall survival. The re-transplantation of tumor cells into mice that survived the primary tumor challenge after primary vaccination led to the complete inhibition of tumor progression in all mHTV-treated mice. This showed that mHTV can effectively suppress cancer recurrence. mHTV also increased the number of tumor-infiltrating lymphocytes in the tumor tissues. When mice were implanted with TC-1 tumor cells after mHTV vaccination, most of the immunized mice were protected from the tumor challenge. In conclusion, mHTV showed considerable potential as not only a therapeutic vaccine, by efficiently killing cancer cells, but also as a prophylactic vaccine by enhancing T cell-mediated immune responses. The Brain Korea 21 Plus Program, Partially supported. The Ministry of Food and Drug Safety grant (grant number 22213MFDS421) The National Research Foundation of Korea (NRF) grant (grant number NRF-2021M3E5E3080558)