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

Nanomedicine. 2020 Oct:29:102254. doi: 10.1016/j.nano.2020.102254. Epub 2020 Jun 30.

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.

Keywords: Anti-cytokine active immunization; Fibroblast growth factor-2 (FGF-2); Human papillomavirus (HPV); Therapeutic vaccine; Virus-like particle (VLP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology*
  • Cell Line, Tumor
  • Fibroblast Growth Factor 2 / antagonists & inhibitors
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / immunology*
  • Humans
  • Immunotherapy
  • Mice
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / immunology*
  • Neovascularization, Pathologic / prevention & control
  • Neovascularization, Pathologic / virology
  • Papillomavirus E7 Proteins / antagonists & inhibitors
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / immunology*
  • Papillomavirus Vaccines / immunology
  • Papillomavirus Vaccines / pharmacology*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Vaccination

Substances

  • Cancer Vaccines
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • oncogene protein E7, Human papillomavirus type 16
  • Fibroblast Growth Factor 2