Intratumoral Expression of MIP-1β Induces Antitumor Responses in a Pre-Established Tumor Model through Chemoattracting T Cells and NK Cells  

作　　者：XiaolingLuo YizhiYu AnminLiang YuanXie ShuxunLiu JunGuo WenyaWang RunziQi HuazhangAn MinghuiZhang HongmeiXu ZhenhongGuo XuetaoCao 

机构地区：[1]TumorExperimentApartment,AffiliatedTumorHospital,GuangxiMedicalUniversity,Nanning530021.China [2]InstituteofImmunology,SecondMilitaryMedicalUniversity,Shanghai200433,China

出　　处：《Cellular & Molecular Immunology》2004年第3期199-204,共6页中国免疫学杂志（英文版）

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).

摘　　要：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.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.

关 键 词：AdhMIP-1β TRANSFECTION gene therapy CT26 colorectal adenocarcinoma antitumor immunity 

分 类 号：R392[医药卫生—免疫学]