'Survival gene' Bcl-xl potentiates DNA-raised antitumor immunity

Gene Ther. 2005 Oct;12(20):1517-25. doi: 10.1038/sj.gt.3302584.

Abstract

T-cell priming is strongly affected by the longevity of antigen-bearing dendritic cells (DCs), which are typically short-lived in lymphoid tissues. 'Survival gene' Bcl-xl is critical for the lifespan of DCs in vivo. Here, we showed that in vivo coadministration of Bcl-xl under control of the DC-specific promoter (CD11c-Bcl-xl) and TRP2hsp70 DNA prolonged T-cell stimulation by DCs and augmented TRP2-specific-IFN-gamma-producing CD8+ T-cell responses. Consistent with these findings, enhanced protection and significant therapeutic immunity to B16 melanoma was generated by this coimmunization strategy, which also augmented therapeutic immunity to GL-26 tumor. In this B16 melanoma model, results from animal experiments with depletion of immune cells indicate that CD8+ T cells and NK cells are important in the antitumor immunity induced by this coimmunization strategy. These observations suggest that 'survival gene' Bcl-xl potentiates the magnitude of antigen-specific-CD8+ T-cell responses and the efficacy of antitumor immunity induced by DNA vaccine, and is relevant for the design of in vivo targeted DC-based vaccine strategies to improve immunity against cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Autoantigens
  • CD11c Antigen / genetics
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / administration & dosage*
  • Dendritic Cells / immunology
  • Female
  • Genetic Therapy / methods*
  • Glioma / immunology
  • Glioma / therapy
  • HSP70 Heat-Shock Proteins / genetics
  • Intramolecular Oxidoreductases / genetics
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Time Factors
  • Vaccines, DNA / administration & dosage*
  • bcl-X Protein / genetics*

Substances

  • Antigens, Neoplasm
  • Autoantigens
  • CD11c Antigen
  • Cancer Vaccines
  • HSP70 Heat-Shock Proteins
  • Vaccines, DNA
  • bcl-X Protein
  • Intramolecular Oxidoreductases
  • dopachrome isomerase