行政院國家科學委員會專題研究計畫期中進度報告:NK細胞受不表現MHC且生產TGF-b之CTVT腫瘤中之細胞素的影響,並開發治療不表現MHC且生產TGF-b腫瘤的基因(2/3)
Date Issued
2004
Date
2004
Author(s)
朱瑞民
DOI
922313B002130
Abstract
Lowering the expression of major histocompatibility complex (MHC) molecules
is one way tumors evade host immune surveillance. Natural killer (NK) cells are
activated by low MHC expression. However, in many tumors, NK cell cytotoxicity is
severely suppressed. Immunogene therapy with plasmid IL-6 and plasmid IL-15
(pIL6/pIL15) stimulated NK cells. The plasmids were delivered by muscle
electroporation. IL-6 antagonized the inhibitory effect of TGF-β on NK cell
cytotoxicity and IL-15 promoted NK cell cytotoxicity. In cell cultures, treatment with
IL-6/IL-15 effectively relieved the inhibitory effect of TGF-β and activated NK cell
cytotoxicity. IL-6 or IL-15 alone did not enhance or only moderately promoted NK cell
cytolytic activity. In BALB/c mice, electroporation with pIL-6/pIL-15 increased the
ratio of NK cells in the spleen and promoted NK cell cytotoxicity. pIL-6 or pIL-15
alone did not have a significant effect. In C.B-17 SCID mice, gene therapy with
pIL-6/pIL-15 strongly inhibited the establishment, and the growth of established canine
transmissible venereal tumor (CTVT), a tumor with low MHC expression and high
TGF-β secretion. Treatment with anti-asialo GM-1 antibody depleted NK cells and
restored tumorigenicity. We demonstrated that the anti-TGF-β effect of IL-6 was
essential, but that stimulation of NK cell cytotoxicity by IL-15 also was necessary to
effectively suppress tumor growth. Both IL-6 and IL-15 should be included in a
3
therapeutic regimen against tumors with low MHC expression and high TGF-β
secretion.
Publisher
臺北市：國立臺灣大學獸醫學系暨研究所
Type
report
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