A therapeutic HPV16 E7 vaccine in combination with active anti-FGF-2 immunization synergistically elicits robust antitumor immunity in mice.

ABSTRACT

FGF-2 accumulates in many tumor tissues and is closely related to the development of tumor angiogenesis and the immunosuppressive microenvironment. This study aimed to investigate whether active immunization against FGF-2 could modify antitumor immunity and enhance the efficacy of an HPV16 E7-specific therapeutic vaccine. Combined immunization targeting both FGF-2 and E7 significantly suppressed tumor growth, which was accompanied by significantly increased levels of IFN-γ-expressing splenocytes and effector CD8 T cells and decreased levels of immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells(MDSCs) in both the spleen and tumor; in addition, the levels of FGF-2 and neovascularization in tumors were decreased in the mice receiving the combined immunization, and tumor cell apoptosis was promoted. The combination of an HPV16 E7-specific vaccine and active immunization against FGF-2 significantly enhances antitumor immune responses in mice with TC-1 tumors, indicating a promising strategy for tumor immunotherapy.