A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer
A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer
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DOI：
10.1158/1078-0432.ccr-06-0114
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发表时间：
2006-10-15
影响因子：
11.5
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
--
作者：
Motohashi, Shinichiro;Ishikawa, Aki;Nakayama, Toshinori
目的：携带恒定V alpha 24 J alpha Q抗原受体的人V alpha 24自然杀伤T（V alpha 24 NKT）细胞被糖脂配体α-半乳糖神经酰胺（alpha GalCer; KRN 7000）以CD 1d依赖性方式激活。用α GalCer和白介素-2活化的人V α 24 NK细胞已显示产生大量细胞因子，如IFN-γ，并且还对各种肿瘤细胞系发挥有效的杀伤活性。我们进行了一项自体活化V α 24 NKT细胞治疗的I期研究。实验设计：晚期或复发性非小细胞肺癌患者接受静脉注射活化V α 24 NKT细胞（水平1：1 × 107/m2和水平2：5 × 107/m2），以测试这种治疗策略的安全性、可行性和临床反应。结果：6例患者入选本研究。本研究期间，在任何患者中均未观察到严重不良事件。在第一次和第二次注射活化V α 24 NKT细胞后，在接受水平2剂量活化V α 24 NKT细胞的三个病例中的两个中观察到外周血V α 24 NKT细胞数量增加。在接受水平2剂量的所有3例病例中，给予活化V α 24 NKT细胞后，外周血单核细胞中IFN-γ产生细胞的数量增加。没有病人被发现符合标准的部分或完全respons.Conclusions：与活化V α 24 NKT细胞管理的临床试验是耐受性良好，进行安全的轻微不良事件，即使在晚期疾病的患者。
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.