NATURAL-KILLER-CELL STIMULATORY FACTOR (NKSF) AUGMENTS NATURAL-KILLER-CELL AND ANTIBODY-DEPENDENT TUMORICIDAL RESPONSE AGAINST COLON-CARCINOMA CELL-LINES

NATURAL-KILLER-CELL STIMULATORY FACTOR (NKSF) AUGMENTS NATURAL-KILLER-CELL AND ANTIBODY-DEPENDENT TUMORICIDAL RESPONSE AGAINST COLON-CARCINOMA CELL-LINES
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DOI:
10.1016/0022-4804(91)90211-4
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发表时间:
1991-04-01
影响因子:
2.2
通讯作者:
DALY, JM
DALY, JM
中科院分区:
医学3区
文献类型:
--
作者:
LIEBERMAN, MD;SIGAL, RK;DALY, JM

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生物反应调节剂可增强自然杀伤(NK)细胞和抗体依赖性杀瘤机制,从而改善结直肠癌的治疗。本研究探讨了最近发现的细胞因子纯化的上清的EB病毒转化的B-淋巴母细胞样细胞系(RPMI-8866),自然杀伤细胞刺激因子(NKSF),对NK和抗体依赖性细胞的细胞毒性(ADCC)的人结肠腺癌细胞系的影响。在存在或不存在NKSF(3.6 pM)或白细胞介素-2(1 nM)的情况下培养人外周血淋巴细胞24小时。分析培养的淋巴细胞对铬-51标记的结肠癌靶SW 1116、498 LI和WC 1的裂解潜力。在6小时细胞毒性试验中检测NKSF处理或对照PBL效应物之前,通过将铬-51标记的SW 1116或WC 1靶标与单克隆抗体CO 17 -1A(一种与胃肠道癌相关细胞抗原反应的IgG 2a抗体)或对照小鼠IgG孵育来测量ADCC。NKSF显著增强结肠癌和NK抗性淋巴瘤细胞系的NK细胞溶解,并且在摩尔基础上,在产生NK细胞毒性方面比白细胞介素-2强约300倍。此外,NKSF显著增强淋巴细胞介导的针对结肠癌靶点的ADCC,并且NKSF与抗体CO 17 -1A的组合对淋巴细胞杀肿瘤能力具有累加效应。因此,NKSF可能在结肠癌的治疗中具有潜在的作用。
The therapy of colorectal cancer may be improved by biologic response modifiers that enhance natural killer (NK) cell and antibody-dependent tumoricidal mechanisms. This study examined the effect of a recently discovered cytokine purified from the supernatant of an Ebstein-Barr virus-transformed B-lymphoblastoid cell line (RPMI-8866), natural killer cell stimulatory factor (NKSF), on NK and antibody-dependent cellular cytotoxicity (ADCC) of human colon adenocarcinoma cell lines. Human peripheral blood lymphocytes were cultured for 24 hr in the presence or absence of NKSF (3.6 pM) or interleukin-2 (1 nM). The cultured lymphocytes were analyzed for lytic potential toward chromium-51-labeled colon carcinoma targets SW 1116, 498 LI, and WC 1. ADCC was measured by incubating chromium-51-labeled SW 1116 or WC 1 targets with the monoclonal antibody CO17-1A, an IgG2a antibody reactive with gastrointestinal cancer-associated cell antigen, or control mouse IgG prior to testing NKSF-treated or control PBL effectors in a 6-hr cytotoxicity assay. NKSF significantly enhanced NK cytolysis of colon carcinoma and NK-resistant lymphoma cell lines, and on a molar basis was approximately 300 times more potent than interleukin-2 in generating NK cytotoxicity. Furthermore, NKSF significantly augmented lymphocyte-mediated ADCC against colon carcinoma targets, and the combination of NKSF with the antibody CO17-1A had an additive effect on lymphocyte tumoricidial capacity. Thus, NKSF may have a potential role in the treatment of colon cancer.