More than chemotaxis: a new anti-tumor DC vaccine modified by rAAV2-SLC

Mol Immunol. 2007 Jul;44(15):3797-804. doi: 10.1016/j.molimm.2007.03.026. Epub 2007 May 22.

Abstract

Secondary lymphoid tissue chemokine (SLC) is strongly expressed in secondary lymphoid organs. Its ability to facilitate chemotaxis of both dendritic cells (DC) and T cells makes it a promising candidate for cancer therapy. In this study, we modified a BMDC vaccine by incorporating the SLC mature peptide gene. The efficacy of this vaccine was evaluated using a mouse hepatocellular carcinoma (HCC) model, with rAAV2 as the gene delivery vector. The rAAV2 encoding SLC (rAAV2-SLC) transfected immature BMDCs at high efficiency and the anti-tumor effects of SLC gene modified BMDCs (rAAV2-SLC/BMDC) were evaluated. In addition, rAAV2-SLC/BMDC vaccine injected directly into tumors attracted more CD4(+) and CD8(+) T lymphocytes into tumors and showed stronger anti-tumor effects than footpad delivery. Moreover, we found that the phenotypic expression of MHC II, the secretion of IL-12 and IFN-gamma, and T cell stimulation were increased in vitro following treatment with rAAV2-SLC/BMDC vaccine and these responses were inhibited by PTX. In vivo, PTX also inhibited the anti-tumor effects of the vaccine. The results suggest that the expression of SLC by rAAV2-SLC/BMDC plays more than a chemotactic role in anti-tumor responses, thus these studies further demonstrate that SLC has potential to be valuable in cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Chemokine CCL21
  • Chemokines, CC / immunology*
  • Chemotaxis / drug effects
  • Chemotaxis / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dependovirus / genetics*
  • Female
  • Liver Neoplasms, Experimental / prevention & control*
  • Mice
  • Mice, Nude
  • Pertussis Toxin / pharmacology
  • Transduction, Genetic
  • Transfection

Substances

  • Cancer Vaccines
  • Ccl21c protein, mouse
  • Chemokine CCL21
  • Chemokines, CC
  • Pertussis Toxin