Anti-ganglioside GM(2) monoclonal antibody-dependent killing of human lung cancer cells by lymphocytes and monocytes
Anti-ganglioside GM(2) monoclonal antibody-dependent killing of human lung cancer cells by lymphocytes and monocytes
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DOI：
10.1111/j.1349-7006.1996.tb00251.x
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发表时间：
1996-05-01
期刊：
影响因子：
--
通讯作者：
Sone, S
中科院分区：
文献类型：
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作者：
Hanibuchi, M;Yano, S;Sone, S
神经节苷脂GM（2）（GM（2））经常出现在神经内分泌起源的人类癌症的细胞表面。抗GM（2）的鼠-人嵌合单克隆抗体（mAb），KM 966，先前被发现可促进人血单核细胞（MNC）溶解各种癌细胞。在这项研究中，我们分析了负责嵌合单克隆抗体依赖性细胞介导的细胞毒性（ADCC）对小细胞肺癌（SCLC）细胞的效应细胞，并检查各种细胞因子对ADCC活性的增强作用。4 h Cr-51释放法测定ADCC活性。通过离心淘洗从同一健康供体的外周血MNC分离高度纯化的淋巴细胞（>99%）和单核细胞（>90%）。KM 966以剂量依赖方式诱导淋巴细胞和单核细胞介导的SCLC细胞溶解，以各种细胞因子[白细胞介素（IL）-2，IL-12和干扰素-γ]预处理淋巴细胞和巨噬细胞集落刺激因子预处理单核细胞显著增强KM 966 mAb存在下对SCLC细胞的杀伤活性。KM 966对非小细胞肺癌细胞的溶解作用与GM（2）表达水平成正比。这些发现表明，KM 966 mAb与细胞因子的联合治疗可能有助于通过ADCC反应在体内杀死表达GM（2）的肺癌细胞。
Ganglioside GM(2) (GM(2)) frequently appears on the cell surface of human cancers of neuroendocrine origin. A mouse-human chimeric monoclonal antibody (mAb), KM966, against GM(2) was previously found to promote the lysis of various cancer cells by human blood mononuclear cells (MNC). In this study, we analyzed the effector cells responsible for the chimeric mAb-dependent cell-mediated cytotoxicity (ADCC) against small cell lung cancer (SCLC) cells and examined the enhancing effect of various cytokines on the ADCC activity. The ADCC activity was assessed by 4-h Cr-51 release assay. Highly purified lymphocytes (>99%) and monocytes (>90%) were separated by centrifugal elutriation from peripheral blood MNC of the same healthy donor. KM966 induced lysis of SCLC cells mediated by both lymphocytes and monocytes to similar extents, in a dose-dependent manner, Pretreatment of lymphocytes with various cytokines [interleukin (IL)-2, IL-12 and interferon-gamma] and that of monocytes with macrophage-colony-stimulating factor significantly augmented the killer activity against SCLC cells in the presence of KM966 mAb. KM966 was also effective for the lysis of non-small cell lung cancer cells in direct proportion to the GM(2) expression levels. These findings suggest that combined treatment of KM966 mAb with cytokines may be therapeutically useful for in vivo killing of lung cancer cells expressing GM(2) through the ADCC reaction.