title: Intratumoral expression of MIP-1beta induces antitumor responses in a pre-established tumor model through chemoattracting T cells and NK cells.
abstract: Direct intratumoral introduction of therapeutic or regulatory genes is a developing technology with potential application for cancer gene therapy. Macrophage inflammatory protein-1 beta (MIP-1beta) 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-1beta) carrying the human MIP-1beta gene. 24 h post-transfection, hMIP-1beta levels reached approximately 980 pg/ml in supernatants of 10(6) hMIP-1beta-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-1beta significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice. Intratumoral hMIP-1beta gene transfer also induced powerful tumor-specific CTL responses in vivo. The therapeutic effects of hMIP-1beta gene therapy were greatly reduced following in vivo depletion of both CD4(+) and CD8(+) T 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-1beta-induced antitumor responses. These results suggest that intratumoral expression of hMIP-1beta has the potential effect to induce host antitumor immunity and may prove to be a useful form of cancer gene therapy.
authors.affiliation: Tumor Experiment Department, Affiliated Tumor Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Luo
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Yu
authors.forename: Anmin
authors.initials: A
authors.lastname: Liang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
authors.forename: Shuxun
authors.initials: S
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.forename: Runzi
authors.initials: R
authors.lastname: Qi
authors.forename: Huazhang
authors.initials: H
authors.lastname: An
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xu
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Guo
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D000256:Adenoviridae; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D054407:Chemokine CCL4; D015179:Colorectal Neoplasms / Q000382:microbiology* / Q000473:pathology / Q000628:therapy; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation / Q000379:methods; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins