Intratumoral expression of MIP-1beta induces antitumor responses in a pre-established tumor model through chemoattracting T cells and NK cells.
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.
Luo
Xiaoling
X
Tumor Experiment Department, Affiliated Tumor Hospital, Guangxi Medical University, Nanning 530021, China.
Yu
Yizhi
Y
Liang
Anmin
A
Xie
Yuan
Y
Liu
Shuxun
S
Guo
Jun
J
Wang
Wenya
W
Qi
Runzi
R
An
Huazhang
H
Zhang
Minghui
M
Xu
Hongmei
H
Guo
Zhenhong
Z
Cao
Xuetao
X
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
D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins