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[关于使用重组白细胞介素-2的过继性免疫疗法的研究]

[Studies on adoptive immunotherapy using recombinant interleukin 2].

作者信息

Sugiyama Y, Takao H, Saji S, Sakata K

出版信息

Gan To Kagaku Ryoho. 1986 Apr;13(4 Pt 2):1307-13.

PMID:3488028
Abstract

Lymphokine activated killer (LAK) cells derived from normal subjects were examined as to the following points: 1) monoclonal analysis of LAK, 2) cytotoxic ability of LAK, 3) effect on LAK cytotoxic ability of the presence in the medium of either serum obtained from gastric cancer patients or nonspecific immunosuppressive factors (ferritin, IAP, AFP), 4) effect, on induction of their cytotoxicity, of the presence in the medium during culture of sera from gastric cancer patients, simulating the conditions of in vivo administration and 5) augmentation of cytotoxic ability of LAK by simultaneous IL2 administration. The following results were obtained. 1) Monoclonal marker analysis of LAK revealed that the ratios of OKT3+, OKT4+, OKT8+ and OKIa1+ lymphocytes were all significantly higher than those in peripheral blood lymphocytes (PBL). 2) Cytotoxic ability of LAK against various tumor cell lines (MKN-28, MKN-45, KATOIII, PC-10 and K562) was found to be higher than that of PBL. 3) Addition to medium of ferritin, IAP or AFP significantly reduced the cytotoxic ability of both PBL and LAK against various tumor cell lines. However, the degree of reduction was significantly milder in the case of LAK than in PBL. 4) The cytotoxicity-suppressing effects of gastric cancer sera (untreated, at stages III and IV) were significantly milder in the case of LAK than in PBL. 5) When gastric cancer serum was added to medium, instead of normal AB serum during induction of LAK, its cytotoxic ability against various tumor cell lines was significantly reduced. Its cytotoxic ability was nevertheless significantly higher than that of PBL. 6) When IL2 was added to medium during cytotoxicity assay, cytotoxic ability of LAK was augmented. When LAK was cultured for 1 hour before assay in fresh medium containing 1,000 U/ml IL2, its cytotoxic ability was further augmented.

摘要

对来自正常受试者的淋巴因子激活的杀伤(LAK)细胞进行了以下几点研究:1)LAK的单克隆分析;2)LAK的细胞毒性能力;3)胃癌患者血清或非特异性免疫抑制因子(铁蛋白、IAP、AFP)存在于培养基中对LAK细胞毒性能力的影响;4)模拟体内给药条件,在培养过程中培养基中存在胃癌患者血清对其细胞毒性诱导的影响;5)同时给予IL2对LAK细胞毒性能力的增强作用。获得了以下结果。1)LAK的单克隆标志物分析显示,OKT3 +、OKT4 +、OKT8 +和OKIa1 +淋巴细胞的比例均显著高于外周血淋巴细胞(PBL)。2)发现LAK对各种肿瘤细胞系(MKN - 28、MKN - 45、KATOIII、PC - 10和K562)的细胞毒性能力高于PBL。3)向培养基中添加铁蛋白、IAP或AFP可显著降低PBL和LAK对各种肿瘤细胞系的细胞毒性能力。然而,LAK的降低程度明显比PBL轻。4)LAK对胃癌血清(未经处理,III期和IV期)的细胞毒性抑制作用明显比PBL轻。5)在LAK诱导过程中,用胃癌血清代替正常AB血清添加到培养基中时,其对各种肿瘤细胞系的细胞毒性能力显著降低。然而,其细胞毒性能力仍显著高于PBL。6)在细胞毒性测定期间向培养基中添加IL2时,LAK的细胞毒性能力增强。当LAK在含有1000 U/ml IL2的新鲜培养基中测定前培养1小时时,其细胞毒性能力进一步增强。

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