Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study
Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study
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DOI：
10.1007/s00262-006-0199-6
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发表时间：
2007-04-01
影响因子：
5.8
通讯作者：
Toma, Hiroshi
中科院分区：
文献类型：
--
作者：
Kobayashi, Hirohito;Tanaka, Yoshimasa;Toma, Hiroshi
目的虽然各种类型的免疫治疗已被用于改善晚期肾细胞癌（RCC）患者的预后，但使用γ-δ（γ δ）T细胞的过继免疫治疗尚未尝试。在这项研究中，我们设计了一项使用体外活化的γ δ T细胞对晚期RCC进行过继免疫治疗的初步研究，以评估这项研究的安全性和可能的抗肿瘤效果。实验设计对根治性肾切除术后的晚期RCC患者通过静脉输注给予玻璃体活化的自体γ δ T细胞，每周或每2周，6-12次，注射70 JRU的teceleukin评估不良事件、抗肿瘤作用和免疫监测。以CT扫描肿瘤倍增时间（DT）为评价指标，流式细胞术检测免疫指标。最常见的不良事件是发热、全身乏力和肝胆酶升高，但未见严重不良事件。延长肿瘤DT被认为是在五个病人中的三个，这三个病人表现出在外周血中的γ δ T细胞的数量增加，也是一个高反应的抗原在vitro.Conclusions的结果表明，过继免疫治疗使用在体外激活自体γ δ T细胞是耐受性良好，诱导抗肿瘤作用。
Purpose Although various types of immunotherapy have been used to improve the prognosis of patients with advanced renal cell carcinoma (RCC), adoptive immunotherapy using gamma-delta (gamma delta) T cells has not yet been tried. In this study, we designed a pilot study of adoptive immunotherapy using in vitro activated gamma delta T cells against advanced RCC to evaluate the safety profile and possible anti-tumor effects of this study.Experimental design Patients with advanced RCC after radical nephrectomy were administered via intravenous infusion in vitro-activated autologous gamma delta T cells every week or every 2 weeks, 6-12 times, with 70 JRU of teceleukin. Adverse events, anti-tumor effects and immunomonitoring were assessed. The anti-tumor effects were evaluated according to tumor doubling time (DT) by computed tomography (CT) and immunomonitoring was performed by flow cytometric analysis.Results Seven advanced RCC patients were entered in this study. The most common adverse events were fever, general fatigue and elevation of hepatobiliary enzymes, but no severe adverse events were seen. Prolongation of tumor DT was seen in three out of five patients; these three patients showed an increase in the number of gamma delta T cells in peripheral blood and also a high response to the antigen in vitro.Conclusions The results indicated that adoptive immunotherapy using in vitro-activated autologous gamma delta T cells was well tolerated and induced anti-tumor effects.