Establishment, Characterization, and Successful Adaptive Therapy Against Human Tumors of NKG Cell, a New Human NK Cell Line
Establishment, Characterization, and Successful Adaptive Therapy Against Human Tumors of NKG Cell, a New Human NK Cell Line
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DOI：
10.3727/096368911x580536
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
--
作者：
Cheng, Min;Ma, Juan;Tian, Zhigang
自然杀伤（NK）细胞在针对某些人类癌症的过继性细胞免疫治疗中发挥重要作用。本研究旨在建立一种新的人NK细胞系，并研究其在过继性肿瘤免疫治疗中的作用。收集54例患者的外周血样品以建立NK细胞系。从一名中国男性急进性非霍奇金淋巴瘤患者中建立了一个新的人NK细胞系，命名为NKG。NKG细胞显示LGL形态，并在表型上鉴定为具有CD 16（-）、CD 27（-）、CD 3（-）、α β TCR-、γ δ TCR-、CD 4（-）、CD 8（-）、CD 19（-）、CD 161（-）、CD 45（+）、CXCR 4（+）、CCR 7（+）、CXCR 1（-）和CX 3CR 1（-）的CD 56（亮）NK细胞。NKG细胞显示粘附分子（CD 2、CD 58、CD 11 a、CD 54、CD 11 B、CD 11 c）、一系列活化受体（NKp 30、NKp 44、NKp 46、NKG 2D、NKG 2C）以及细胞溶解相关受体和分子（TRAIL、FasL、颗粒酶B、穿孔素、IFN-γ）的高表达。NKG细胞对肿瘤细胞的杀伤活性高于已建立的NK细胞系NK-92、NKL和YT。NKG细胞毒性取决于NKG 2D和NKp 30的存在。在8戈伊照射下，NKG细胞在体外仍具有较高的细胞毒性和活性，在体内仍具有安全性，但无增殖。此外，经辐照的NKG细胞在体外对人原发性卵巢癌细胞以及在小鼠异种移植模型中对人卵巢癌表现出强细胞毒性。过继转移的NKG细胞显着抑制卵巢肿瘤的生长，降低死亡率和延长生存期，即使在晚期疾病的情况下。在细胞治疗期间，在卵巢肿瘤组织中检测到大量NKG细胞。利用新的人NK细胞系，NKG将是人类癌症过继免疫治疗的有希望的细胞候选者。
Natural killer (NK) cells play important roles in adoptive cellular immunotherapy against certain human cancers. This study aims to establish a new human NK cell line and to study its role for adoptive cancer immunotherapy. Peripheral blood samples were collected from 54 patients to establish the NK cell line. A new human NK cell line, termed as NKG, was established from a Chinese male patient with rapidly progressive non-Hodgkin's lymphoma. NKG cells showed LGL morphology and were phenotypically identified as CD56(bright) NK cell with CD16(-), CD27(-), CD3(-), alpha beta TCR-, gamma delta TCR-, CD4(-), CD8(-), CD19(-), CD161(-), CD45(+), CXCR4(+), CCR7(+), CXCR1(-), and CX3CR1(-). NKG cells showed high expression of adhesive molecules (CD2, CD58, CD11a, CD54, CD11b, CD11c), an array of activating receptors (NKp30, NKp44, NKp46, NKG2D, NKG2C), and cytolysis-related receptors and molecules (TRAIL, FasL, granzyme B, perforin, IFN-gamma). The cytotoxicity of NKG cells against tumor cells was higher than that of the established NK cell lines NK-92, NKL, and YT. NKG cell cytotoxicity depended on the presence of NKG2D and NKp30. When irradiated with 8 Gy, NKG cells were still with high cytotoxicity and activity in vitro and with safety in vivo, but without proliferation. Further, the irradiated NKG cells exhibited strong cytotoxicity against human primary ovarian cancer cells in vitro, and against human ovarian cancer in a mouse xenograft model. The adoptive transfer of NKG cells significantly inhibited the ovarian tumor growth, decreased the mortality rate and prolonged the survival, even in cases of advanced diseases. A number of NKG cells were detected in the ovarian tumor tissues during cell therapy. In use of the new human NK cell line, NKG would a promising cellular candidate for adoptive immunotherapy of human cancer.