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[采用淋巴因子激活的杀伤细胞(LAK 细胞)和白细胞介素 -2 对转移性肾细胞癌进行过继性免疫治疗的研究。I. 在无血清培养基中孵育产生 LAK 细胞]

[Study of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and interleukin-2 for metastatic renal cell carcinoma. I. Generation of LAK cells by incubation in serum-free medium].

作者信息

Nomura K, Fujioka T

机构信息

Department of Urology, Iwate Medical University School of Medicine.

出版信息

Nihon Hinyokika Gakkai Zasshi. 1993 May;84(5):822-30. doi: 10.5980/jpnjurol1989.84.822.

Abstract

Investigation into the clinical application of LAK cells for treating renal cell carcinoma was carried out. LAK cells were induced from peripheral blood mononuclear cells of healthy adults or renal cell carcinoma patients by incubation of peripheral blood mononuclear cells in complete medium (RMPI1640 containing 10% heat-inactivated human AB serum) or serum-free medium (AIM-V) supplemented with IL-2. Then the characteristics of the LAK cells thus produced were studied. When cultured in complete medium, peripheral blood mononuclear cells isolated from healthy adults, recovered to 60% of the initial level on day 4 of incubation. Both NK and LAK activity were markedly enhanced before day 4. On day 4, a similar number of peripheral blood mononuclear blood cells and a similar cytotoxicity were observed in serum-free culture. The cells with a high growth rate during the 4 days of incubation were CD25, HLA-DR, CD3, CD16 cells in both cultures. The supernatant of LAK generation cultures had detectable levels of interferon (IFN)-gamma, interleukin (IL)-1 beta, and tumor necrosis factor (TNF)-alpha on day 4. IFN-gamma and IL-1 beta both showed significant concentrations in the LAK culture supernatant, which increased progressively with further culture. TNF-alpha was not produced by LAK cells alone. IFN-gamma and IL-beta production by the LAK cells was enhanced by stimulation with the Caki-1, ACHN and K-562 tumor cell lines, while TNF-alpha production was stimulated by Caki-1 and K-562 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

开展了关于LAK细胞治疗肾细胞癌的临床应用研究。通过将外周血单个核细胞在完全培养基(含10%热灭活人AB血清的RMPI1640)或添加白细胞介素-2的无血清培养基(AIM-V)中培养,从健康成年人或肾细胞癌患者的外周血单个核细胞诱导生成LAK细胞。然后研究了由此产生的LAK细胞的特性。在完全培养基中培养时,从健康成年人分离的外周血单个核细胞在培养第4天恢复到初始水平的60%。在第4天之前,自然杀伤(NK)活性和LAK活性均显著增强。在第4天,无血清培养中观察到数量相似的外周血单个核血细胞和相似的细胞毒性。在两种培养物中,培养4天期间生长速率高的细胞是CD25、HLA-DR、CD3、CD16细胞。LAK细胞生成培养物的上清液在第4天可检测到干扰素(IFN)-γ、白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α水平。IFN-γ和IL-1β在LAK培养上清液中均显示出显著浓度,并随着进一步培养而逐渐增加。TNF-α不是由LAK细胞单独产生的。用Caki-1、ACHN和K-562肿瘤细胞系刺激可增强LAK细胞产生IFN-γ和IL-β,而Caki-1和K-562细胞刺激可促进TNF-α的产生。(摘要截短为250字)

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