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Cell Mol Immunol. 2004 Jun;1(3):199-204.

Intratumoral expression of MIP-1beta induces antitumor responses in a pre-established tumor model through chemoattracting T cells and NK cells.

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1
Tumor Experiment Department, Affiliated Tumor Hospital, Guangxi Medical University, Nanning 530021, China.

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.

PMID:
16219168
[Indexed for MEDLINE]
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