期刊
CLINICAL CANCER RESEARCH
卷 12, 期 20, 页码 6079-6086出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-06-0114
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Purpose: Human V alpha 24 natural killer T (V alpha 24 NKT) cells bearing an invariant V alpha 24J alpha Q antigen receptor are activated by a glicolipid ligand a-galactosylceramide (alpha GalCer; KRN7000) in a CD1d-dependent manner. The human V alpha 24 NKTcells activated with alpha GalCer and interleukin-2 have been shown to produce large amounts of cytokines, such as IFN-gamma, and also exerting a potent killing activity against various tumor cell lines. We did a phase I study with autologous activated V alpha 24 NKT cell therapy. Experimental Design: Patients with advanced or recurrent non-small cell lung cancer received i.v. injections of activated V alpha 24 NKTcells (level 1: 1 x 10(7)/m(2) and level 2: 5 x 107/m(2)) to test the safety, feasibility, and clinical response of this therapeutic strategy. Immunomonitoring was also done in all cases. Results: Six patients were enrolled in this study. No severe adverse events were observed during this study in any patients. After the first and second injection of activated V alpha 24 NKTcells, an increased number of peripheral blood V alpha 24 NKTcells was observed in two of three cases receiving a level 2 dose of activated V alpha 24 NKTcells. The number of IFN-gamma-producing cells in peripheral blood mononuclear cells increased after the administration of activated V alpha 24 NKT cells in all three cases receiving the level 2 dose. No patient was found to meet the criteria for either a partial or a complete response. Conclusions: The clinical trial with activated V alpha 24 NKT cell administration was well tolerated and carried out safely with minor adverse events even in patients with advanced diseases.
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