Synergistic antitumor efficacy of combined DNA vaccines targeting tumor cells and angiogenesis

Biochem Biophys Res Commun. 2015 Sep 18;465(2):239-44. doi: 10.1016/j.bbrc.2015.08.003. Epub 2015 Aug 4.

Abstract

To further enhance the antitumor efficacy of DNA vaccine, we proposed a synergistic strategy that targeted tumor cells and angiogenesis simultaneously. In this study, a Semliki Forest Virus (SFV) replicon DNA vaccine expressing 1-4 domains of murine VEGFR2 and IL12 was constructed, and was named pSVK-VEGFR2-GFc-IL12 (CAVE). The expression of VEGFR2 antigen and IL12 adjuvant molecule in 293T cells in vitro were verified by western blot and enzyme-linked immune sorbent assay (ELISA). Then CAVE was co-immunized with CAVA, a SFV replicon DNA vaccine targeting survivin and β-hCG antigens constructed previously. The antitumor efficacy of our combined replicon vaccines was evaluated in mice model and the possible mechanism was further investigated. The combined vaccines could elicit efficient humoral and cellular immune responses against survivin, β-hCG and VEGFR2 simultaneously. Compared with CAVE or CAVA vaccine alone, the combined vaccines inhibited the tumor growth and improved the survival rate in B16 melanoma mice model more effectively. Furthermore, the intratumoral microvessel density was lowest in combined vaccines group than CAVE or CAVA alone group. Therefore, this synergistic strategy of DNA vaccines for tumor treatment results in an increased antitumor efficacy, and may be more suitable for translation to future research and clinic.

Keywords: Angiogenesis; DNA vaccine; Tumor; VEGFR2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Chorionic Gonadotropin, beta Subunit, Human / antagonists & inhibitors
  • Chorionic Gonadotropin, beta Subunit, Human / genetics
  • Chorionic Gonadotropin, beta Subunit, Human / immunology
  • Female
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Immunity, Cellular / drug effects*
  • Immunity, Humoral / drug effects*
  • Immunization
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / immunology
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / prevention & control*
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Replicon
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • Semliki forest virus / genetics
  • Semliki forest virus / metabolism
  • Skin Neoplasms / genetics
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*
  • Survivin
  • Treatment Outcome
  • Vaccines, Combined
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / immunology

Substances

  • Birc5 protein, mouse
  • Cancer Vaccines
  • Chorionic Gonadotropin, beta Subunit, Human
  • Inhibitor of Apoptosis Proteins
  • Repressor Proteins
  • Survivin
  • Vaccines, Combined
  • Vaccines, DNA
  • Interleukin-12
  • Kdr protein, mouse
  • Vascular Endothelial Growth Factor Receptor-2