Adenoviral gene transfer of stromal cell-derived factor-1 to murine tumors induces the accumulation of dendritic cells and suppresses tumor growth. Academic Article uri icon

Overview

MeSH

  • Adenocarcinoma
  • Adenoviridae
  • Animals
  • Carcinoma, Lewis Lung
  • Cell Growth Processes
  • Chemokine CXCL12
  • Colonic Neoplasms
  • Female
  • Gene Transfer Techniques
  • Genetic Vectors
  • Immunity, Cellular
  • Lymph Nodes
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout

MeSH Major

  • Chemokines, CXC
  • Dendritic Cells
  • Neoplasms, Experimental

abstract

  • The human CXC chemokine, stromal cell-derived factor 1 (SDF-1alpha), is known to function in vitro as a chemotactic factor for lymphocytes, monocytes, and dendritic cells. In the context that dendritic cells are powerful antigen-presenting cells, we hypothesized that adenoviral gene transfer of SDF-1alpha to tumors might inhibit growth of preexisting tumors through attracting dendritic cells to the tumor. AdSDF-1alpha mediated the expression of SDF-1alpha mRNA and protein in A549 cells in vitro, and the supernatant of the AdSDF-1alpha-infected A549 cells showed chemotactic activity for dendritic cells. When syngeneic murine CT26 colon carcinoma tumors (BALB/c) and B16 melanoma and Lewis lung cell carcinoma (C57Bl/6) were injected with AdSDF-1alpha (5 x 10(8) plaque-forming units), there was an accumulation of dendritic cells and CD8(+) cells within the tumor and significant inhibition of tumor growth compared with tumors injected with PBS or AdNull (control vector). The injection of AdSDF-1alpha into tumors induced the inflammatory enlargement and the accumulation of dendritic cells in the draining lymph node. Intratumoral AdSDF-1alpha administration elicited tumor-specific CTLs and adoptive transfer of splenocytes from AdSDF-1alpha-treated mice resulted in the elongation of survival after tumor challenge. Interestingly, in wild-type and CD4(-/-) mice but not in CD8(-/-) mice, AdSDF-1alpha inhibited the growth of the tumor. These observations suggest that adenoviral gene transfer of SDF-1alpha may be a useful strategy to accumulate dendritic cells in tumors and evoke antitumor immune responses to inhibit tumor growth.

publication date

  • April 1, 2006

has subject area

  • Adenocarcinoma
  • Adenoviridae
  • Animals
  • Carcinoma, Lewis Lung
  • Cell Growth Processes
  • Chemokine CXCL12
  • Chemokines, CXC
  • Colonic Neoplasms
  • Dendritic Cells
  • Female
  • Gene Transfer Techniques
  • Genetic Vectors
  • Immunity, Cellular
  • Lymph Nodes
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasms, Experimental

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-05-1493

PubMed ID

  • 16585175

Additional Document Info

start page

  • 3513

end page

  • 3522

volume

  • 66

number

  • 7