SA-4-1BBL serves as an effective immunostimulatory component of HPV-16 E7 protein based therapeutic vaccine in a mouse model of cervical cancer (131.21)

Abstract Cervical cancer is a major health problem in women worldwide. Current prophylactic vaccines are ineffective in therapeutic settings. Therefore, there is an acute need for the development of therapeutic vaccines. The HPV E7 oncoprotein is consistently expressed in cervical cancer, required for the maintenance of the transformed phenotype, and is not subjected to antigenic drift. However, the low antigenicity of this protein may require potent adjuvants for therapeutic efficacy. We have recently generated a novel form of the 4-1BBL costimulatory molecule chimeric with core streptavidin (SA-4-1BBL) and demonstrated its pleiotropic effects in soluble from on various cells of the immune system. We herein tested the utility of SA-4-1BBL as the immunomodulatory component of HPV-16 E7 recombinant protein based therapeutic vaccine in the E7 expressing TC-1 cervical cancer mouse model as a prelude to clinical trials. A single subcutaneous vaccination was effective in eradicating established TC-1 tumors in ~70% of mice. The therapeutic efficacy of the vaccine was associated with robust primary and memory CD4+ and CD8+ T cell responses, incresed CD8+ T cells and decreased T reg cells in tumor, enhanced NK cell killing, and generation of IFN-γ and IL-2 responses. Taken together, these data demonstrate the utility of SA-4-1BBL as a new class of immunomodulator for the development of therapeutic vaccines against cancer and chronic infections.