Anti-glioma effect of intracranial vaccination with tumor cell lysate plus flagellin in mice

Vaccine. 2018 Dec 18;36(52):8148-8157. doi: 10.1016/j.vaccine.2018.04.053. Epub 2018 Nov 16.

Abstract

The adjuvant effects of flagellin on regulation of immune response have been proved; whether flagellin could assist tumor cell lysate (TCL) to enhance anti-glioma immunity remains to be investigated. This study tests a hypothesis that therapeuticly intracranial administration with flagellin plus TCL enhances the effects of specific immunotherapy on glioma in mice. In this study, GL261 cells were transferred into C57BL/6 mice and the GL261-bearing mice were subcutaneously or intracranially inoculated with flagellin plus TCL, flagellin, TCL or saline. Our results showed that prophylacticly subcutaneous administration with TCL and flagellin could induce potent cytotoxic T lymphocyte (CTL) and prolong the survival of GL261-bearing mice significantly, but therapeuticly subcutaneous administration failed to. However, therapeuticly intracranial administration of TCL plus flagellin could prolong the survival. Moreover, intracranial administration of flagellin could recruit CD4+ T cells and CD8+ T cells to brain tissues, induce proliferation of natural killer (NK) cells, CD4+ T cells and CD8+ T cells in peripheral blood mononuclear cells and induce to splenomegaly. The results suggested that flagellin could be acted as an efficient adjuvant for TCL based vaccine.

Keywords: Adjuvant; Flagellin; Glioma; Tumor cell lysate; Vaccine.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Cell Extracts / immunology
  • Cell Extracts / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Flagellin / administration & dosage
  • Flagellin / immunology*
  • Glioma / immunology*
  • Glioma / therapy*
  • Immunotherapy
  • Killer Cells, Natural / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Cell Extracts
  • Flagellin