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接受联合免疫疗法(白细胞介素-2、α干扰素和自体白细胞介素-2激活淋巴细胞)的转移性肾细胞癌患者免疫参数的调节

Modulation of immune parameters in patients with metastatic renal-cell cancer receiving combination immunotherapy (IL-2, IFN alpha and autologous IL-2-activated lymphocytes).

作者信息

Gratama J W, Schmitz P I, Goey S H, Lamers C H, Stoter G, Bolhuis R L

机构信息

Department of Clinical and Tumor Immunology, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.

出版信息

Int J Cancer. 1996 Jan 17;65(2):152-60. doi: 10.1002/(SICI)1097-0215(19960117)65:2<152::AID-IJC5>3.0.CO;2-Y.

Abstract

We treated 72 patients with metastatic renal-cell cancer according to 2 protocols consisting of two 5-week induction cycles of continuous i.v. high-dose interleukin-2 (IL-2), i.m. interferon-alpha (IFN alpha) and ex vivo IL-2-activated lymphocytes, followed for patients with stable disease (SD), partial response (PR) or complete response (CR) by four 4-week maintenance cycles of IL-2 and IFN alpha. Protocol 2 (55 patients) differed from protocol 1 (17 patients) in (i) the addition of IFN alpha to the first IL-2 infusions in both induction cycles; (ii) the use of Teceleukin IL-2, reconstituted with carrier protein, instead of Proleukin IL-2 without carrier protein. We classified 23 patients with CR and PR as responders (4 in protocol 1 and 19 in protocol 2) and 45 patients with SD and progressive disease as non-responders. Prior to immunotherapy, patients entered into protocol 2 already had higher IFN gamma serum concentrations, higher peripheral blood CD56-,3+ and CD8-,4+ lymphocyte numbers and lower NKK562 activity than those entered into protocol 1. These differences persisted during and after immunotherapy. In line with these observations, ex vivo IL-2-activated lymphocytes had larger proportions of CD56-,3+ and CD8-,4+ lymphocytes and lower NKK562 activity in protocol 2 than in protocol 1. Higher IL-2 serum concentrations were reached during the IL-2 infusion in protocol 2 than in protocol 1. In addition, the immunomodulation in protocol 2 was stronger than in protocol 1 as indicated by higher TNF alpha serum concentrations and a more pronounced eosinophilia. Differences between responders and non-responders treated according to the 2 protocols were not significant, except for the total number of lymphocytes obtained by apheresis, which was higher in responders than in non-responders.

摘要

我们根据2种方案治疗了72例转移性肾细胞癌患者,这2种方案均包含两个为期5周的连续静脉注射高剂量白细胞介素-2(IL-2)、肌肉注射α-干扰素(IFNα)以及体外IL-2激活淋巴细胞的诱导周期,对于疾病稳定(SD)、部分缓解(PR)或完全缓解(CR)的患者,后续给予四个为期4周的IL-2和IFNα维持周期。方案2(55例患者)与方案1(17例患者)的不同之处在于:(i)在两个诱导周期的首次IL-2输注中均添加IFNα;(ii)使用与载体蛋白重构的替西白介素IL-2,而非不含载体蛋白的普乐白介素IL-2。我们将23例CR和PR患者分类为反应者(方案1中有4例,方案2中有19例),将45例SD和疾病进展患者分类为无反应者。在免疫治疗前,进入方案2的患者血清IFNγ浓度更高,外周血CD56⁺、3⁺和CD8⁺、4⁺淋巴细胞数量更多,NKK562活性更低,相比进入方案1的患者。这些差异在免疫治疗期间及之后持续存在。与这些观察结果一致,方案2中体外IL-2激活淋巴细胞的CD56⁺、3⁺和CD8⁺、4⁺淋巴细胞比例更高,NKK562活性更低,相比方案1。方案2中IL-2输注期间达到的血清IL-2浓度高于方案1。此外,方案2中的免疫调节比方案1更强,表现为血清TNFα浓度更高和嗜酸性粒细胞增多更明显。根据这2种方案治疗的反应者和无反应者之间的差异不显著,除了通过单采获得的淋巴细胞总数,反应者高于无反应者。

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