Induction of potent anti-tumor immunity by direct injection of Ad-LIGHT at the site of tumor inoculation

Cytotherapy. 2007;9(4):386-96. doi: 10.1080/14653240701326749.

Abstract

Background: The aim of this study was to observe the therapeutic effects of adenovirus-mediated LIGHT gene transfer in murine B16 melanoma in vivo.

Methods: C57BL/6 mice were inoculated subcutaneously with B16 cells to establish the murine melanoma model. The tumor-bearing mice were injected at the site of tumor inoculation with recombinant adenoviral vectors expressing the murine LIGHT gene. The tumor growth and survival period of tumor-bearing mice were observed. The splenic NK and CTL activity were measured in vitro by lactate dehydrogenase (LDH) release assay. The amounts of cytokines were determined with ELISA kits.

Results: The LIGHT gene could be efficiently transduced into tumor tissue after injection of Ad-LIGHT. Treatment with Ad-LIGHT significantly inhibited the tumor growth and prolonged the survival period of the tumor-bearing mice. The splenic NK and CTL activity of the mice was also enhanced after LIGHT gene transfer. The production of IL-2 and IFN-gamma from lymphocytes derived from mice treated with Ad-LIGHT was increased significantly compared with control groups.

Discussion: Our results indicate that local expression of the LIGHT gene can induce potent anti-tumor immunity and may be a promising treatment strategy for melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cytokines / biosynthesis
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunity / immunology
  • Inflammation
  • Injections
  • Killer Cells, Natural / cytology
  • Melanoma, Experimental / chemically induced
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology*
  • Melanoma, Experimental / therapy
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration / immunology
  • Spleen / cytology
  • T-Lymphocytes, Cytotoxic / cytology
  • Th1 Cells / cytology
  • Transduction, Genetic
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / genetics*
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / metabolism

Substances

  • Cytokines
  • Tumor Necrosis Factor Ligand Superfamily Member 14