Immunotherapy with Cytokine Induced Killer Cells in Solid and Hematopoietic Tumors: Preliminary Data.
Immunotherapy with Cytokine Induced Killer Cells in Solid and Hematopoietic Tumors: Preliminary Data.
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DOI：
10.1182/blood.v106.11.2395.2395
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发表时间：
2005-11
期刊：
影响因子：
20.3
通讯作者：
P. Olioso;R. Giancola;M. Riti;P. Accorsi;A. Spadano;D. Natale;Roberto Rossetti;P. Bartolomeo;A. Iacone
中科院分区：
文献类型：
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作者：
P. Olioso;R. Giancola;M. Riti;P. Accorsi;A. Spadano;D. Natale;Roberto Rossetti;P. Bartolomeo;A. Iacone
CIK 细胞是一种独特的 CD3 + CD56 + 免疫效应细胞群，能够通过 NKG2D 介导的基于穿孔素的机制裂解多种靶向肿瘤细胞。我们根据目前正在进行的 GMP 指南，在难治性淋巴瘤和实体瘤患者中启动了一项试点临床试验。方法：从 PBMNC 中产生 CIK 细胞，并在存在 IFN-γ、随后是 IL-1β、OKT3 和 IL-2 的情况下在 LifeCell 培养袋中孵育。在第 21 天和第 28 天之间评估扩增，并每周进行流式细胞术分析。在治疗前和治疗后对患者进行监测。使用未配对t检验来分析统计显着性。 p值结果：目前入组了10名患者：6名晚期淋巴瘤、3名转移性肾癌和1名肝细胞癌。每名患者转移细胞的中位数为 19 x10 9 (6–37 x10 9 )，输注的 CD3+CD56+ 细胞的绝对数范围为 1 至 16 x10 9 （中位数 5 x10 7 /Kg）。实体瘤患者接受低剂量的 rhIL-2 或 α-干扰素治疗。方案遵守情况非常好，毒性特征也良好。只有 2 名患者在第一个输注周期中出现低烧（5%），但无需抗生素治疗即可迅速缓解。 CIK细胞输注后，患者外周血中PBL、CD3+、CD8+和CD3+CD56+细胞的绝对中位计数显着增加，p值分别为0.034、0.025、0.034和0.038。临床结果似乎很有希望：2 名患者获得完全缓解（1 名转移性肾癌和 1 名肝细胞癌），2 名患者病情稳定（1 名转移性肾癌和 1 名非霍奇金淋巴瘤），中位随访时间为 12 个月（范围 4-14）。结论：这些初步数据表明，CIK 细胞的过继免疫疗法是一种安全的疗法，具有一定的疗效，可显着增强免疫功能，增加效应细胞的绝对数量，且无副作用。如果在更大规模的研究中得到证实，这些有希望的结果可能会对恶性肿瘤的传统治疗策略产生有利的影响。
CIK cells are a unique population of CD3 + CD56 + immune effector cells capable of lysing a broad variety of tumor cells targeted through a perforin based mechanism mediated by NKG2D. We started a pilot clinical trial in patients with refractory lymphoma and solid tumors according to GMP guidelines that is currently ongoing. Methods : CIK cells were generated from PBMNC and incubated in LifeCell culture bags in the presence of IFN-γ followed by IL-1β, OKT3 and IL-2. Expansion was assessed between day 21 and 28 and flow cytometric analysis was performed every week. Patients were monitored before and after treatment. Unpaired t-test was used to analyze for statistical significance. A p-value Results : At present 10 patients are enrolled: 6 advanced lymphomas, 3 metastatic kidney carcinoma and 1 hepatocellular carcinoma. The median number of transferred cells per patient was 19 x10 9 (6–37 x10 9 ) and the absolute number of CD3+CD56+ cells infused ranged from 1 to 16 x10 9 (median value 5 x10 7 /Kg). Patients affected by solid tumors received in association low doses of rhIL-2 or α-interferon. Protocol adherence was excellent and the toxicity profile was favourable. Only 2 patients developed low-grade fever during the first cycle of infusion (5%) but promptly resolved without antibiotic treatment. After CIK cell infusion, in patient’s peripheral blood the absolute median count of PBLs, CD3+, CD8+ and CD3+CD56+ cells significantly increased with a p-value of 0.034, 0.025, 0.034 and 0.038, respectively. Clinical outcome appeared promising: 2 patients had complete response (1 metastatic kidney carcinoma and 1 hepatocellular carcinoma) and 2 patients had stabilization of disease (1 metastatic kidney carcinoma and 1 NHL) with a median follow-up of 12 months (range 4–14). Conclusions : These preliminary data showed that adoptive immunotherapy with CIK cells is a safe therapy with some suggestion of efficacy that significantly enhances immune functions increasing absolute numbers of effector cells without side effects. If confirmed in larger scale studies, these promising results may have a favourable impact on conventional treatment strategy of malignancies.