Adeno-associated virus-mediated local delivery of LIGHT suppresses tumorigenesis in a murine cervical cancer model

J Immunother. 2011 Oct;34(8):581-7. doi: 10.1097/CJI.0b013e31822b9fe0.

Abstract

LIGHT is a tumor necrosis factor superfamily ligand that is considered as a promising candidate for cancer therapy. It has a potent antitumor activity through establishing lymphoid-like tissues inside tumor sites and recruiting naive T cells into the tumor. In this study, we examined the possibility of antitumor activity by expressing LIGHT in cervical cancer (CC) model. A recombinant adeno-associated virus (AAV) vector was chosen for the transfer, based on its transfection efficiency and lack of detectable pathology. In vitro transfer of recombinant AAV vector expressing LIGHT (AAV-LIGHT) stimulated T-lymphocyte proliferation and activation. AAV-mediated gene transfer of LIGHT by intratumoral injection exerted a very potent antitumor effect against preexisting TC-1 cell CC in C57BL/6 mice. This study confirmed that AAV-LIGHT regressed tumor growth by activating cytotoxic T lymphocyte, enhancing infiltration of inflammatory cells in tumor and increasing stimulatory cytokine expression in tumor microenvironment. Therefore, AAV-LIGHT therapy might have potential utility for the treatment of CC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic* / genetics
  • Cell Transformation, Neoplastic* / metabolism
  • Cricetinae
  • Dependovirus / genetics*
  • Disease Models, Animal
  • Female
  • Gene Transfer Techniques
  • Genetic Vectors / genetics*
  • HEK293 Cells
  • Humans
  • Lymphocyte Activation / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Spleen / immunology
  • Spleen / metabolism
  • Transduction, Genetic
  • Tumor Burden / genetics
  • Tumor Burden / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / genetics*
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / metabolism
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • Tumor Necrosis Factor Ligand Superfamily Member 14