Direct intratumoral introduction of therapeutic or regulatory genes is a developing technology with potential application for cancer gene therapy.Macrophage inflammatory protein-I beta(MIP-Iβ)is a chemokine which can...Direct intratumoral introduction of therapeutic or regulatory genes is a developing technology with potential application for cancer gene therapy.Macrophage inflammatory protein-I beta(MIP-Iβ)is a chemokine which can chemoattract immune cells such as T cells.In the present study,murine colorectal adenocarcinoma CT26 cells were transfected with a recombinant adenovirus (AdhMIP-Iβ)carrying the human MIP-Iβ gene.24 h post-transfection,hMIP-1β levels reached approximately 980 pg/ml in supernatants of 10~6 hMIP-Iβ-transfected CT26 cells.Moreover,the supernatants exhibited chemotactic activity for CD8^+ T cells,CD4^+ T cells,NK cells and immature DCs.Intratumoral injection of AdhMIP-Iβ significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice.Intratumoral hMIP-Iβ gene transfer also induced powerful tumor-specific CTL responses in vivo.The therapeutic effects of hMIP-Iβ gene therapy were greatly reduced following in vivo depletion of both CD4^+ and CD8^+ cells,but were unaffected by depletion of single T cell subsets.Immune cell depletion experiments also revealed that NK cells played an important role in hMIP-1β-induced antitumor responses.These results suggest that intratumoral expression of hMIP-1β has the potential effect to induce host antitumor immunity and may prove to be a useful form of cancer gene therapy. Cellular & Molecular Immunology.2004;1(3):199-204.展开更多
基金supported by Grants from National Natural Science Foundation of China(30271202)Natural High Technology Research and Development Program of China(2003AA215040)the National Key Basic Research Program of China(2001CB510002).
文摘Direct intratumoral introduction of therapeutic or regulatory genes is a developing technology with potential application for cancer gene therapy.Macrophage inflammatory protein-I beta(MIP-Iβ)is a chemokine which can chemoattract immune cells such as T cells.In the present study,murine colorectal adenocarcinoma CT26 cells were transfected with a recombinant adenovirus (AdhMIP-Iβ)carrying the human MIP-Iβ gene.24 h post-transfection,hMIP-1β levels reached approximately 980 pg/ml in supernatants of 10~6 hMIP-Iβ-transfected CT26 cells.Moreover,the supernatants exhibited chemotactic activity for CD8^+ T cells,CD4^+ T cells,NK cells and immature DCs.Intratumoral injection of AdhMIP-Iβ significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice.Intratumoral hMIP-Iβ gene transfer also induced powerful tumor-specific CTL responses in vivo.The therapeutic effects of hMIP-Iβ gene therapy were greatly reduced following in vivo depletion of both CD4^+ and CD8^+ cells,but were unaffected by depletion of single T cell subsets.Immune cell depletion experiments also revealed that NK cells played an important role in hMIP-1β-induced antitumor responses.These results suggest that intratumoral expression of hMIP-1β has the potential effect to induce host antitumor immunity and may prove to be a useful form of cancer gene therapy. Cellular & Molecular Immunology.2004;1(3):199-204.
