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

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. C57 mice with fully established TC-1 tumor were immunized with two VLPs targeting HPV16 E7 and FGF-2 respectively, presenting synergistic anti-tumor effects. Tumor growth was significantly suppressed in mice receiving the combined immunization as compared to either VLP immunization. Correspondingly, the responses of tumor specific effector T cells were significantly enhanced in both the spleen and local tumor tissue while levels of immunosuppressive cells including Tregs and MDSCs were decreased. In addition, the neovascularization in tumors were reduced and tumor cell apoptosis was promoted. [Display omitted] •Combined immunization of targeting FGF-2 and HPV E7 produces synergetic suppression on tumor growth;•Combined immunization synergistically boosted systemic antitumor immune responses;•Combined immunization synergistically improved local antitumor immunity in tumor;•Combined immunization synergistically suppresses neovascularization and promotes tumor cell apoptosis.