人单核细胞通过单克隆抗P-糖蛋白抗体依赖性杀伤多药耐药肿瘤细胞
Monoclonal anti-P-glycoprotein antibody-dependent killing of multidrug-resistant tumor cells by human mononuclear cells.
作者信息
Heike Y, Hamada H, Inamura N, Sone S, Ogura T, Tsuruo T
机构信息
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
出版信息
Jpn J Cancer Res. 1990 Nov;81(11):1155-61. doi: 10.1111/j.1349-7006.1990.tb02528.x.
Abstract
Mouse monoclonal antibodies (MRK16 and MRK17) against human multidrug-resistant cancer cell lines were tested for antibody-dependent cytotoxicity mediated by human blood mononuclear cells, using a 4-h 51Cr release assay. MRK16 (IgG2a isotype) was shown to be more effective than MRK17 (IgG1 isotype). Moreover, when four pairs of drug-resistant and their parent sensitive human cancer cells were tested for antibody-dependent cell-mediated cytolysis (ADCC) using MRK16, only the drug-resistant cell lines were susceptible to ADCC reaction. When highly purified lymphocytes (greater than 99%) and monocytes (greater than 97%) were isolated from blood mononuclear cells by centrifugal elutriation and adherence, MRK16 promoted both lymphocyte- and monocyte-mediated tumor cell killing, whereas MRK17 induced only a lymphocyte-mediated ADCC reaction. These results suggest that MRK16 of IgG2a subtype may be a useful therapeutic agent in eradication of drug-resistant cancer cells expressing P-glycoprotein through ADCC reaction.
摘要
利用4小时51铬释放试验，检测了针对人多药耐药癌细胞系的小鼠单克隆抗体（MRK16和MRK17）介导的人血单核细胞抗体依赖性细胞毒性。结果显示，MRK16（IgG2a亚型）比MRK17（IgG1亚型）更有效。此外，当使用MRK16对四对耐药及其亲本敏感的人癌细胞进行抗体依赖性细胞介导的细胞毒作用（ADCC）检测时，只有耐药细胞系对ADCC反应敏感。当通过离心淘析和贴壁从血单核细胞中分离出高度纯化的淋巴细胞（大于99%）和单核细胞（大于97%）时，MRK16促进淋巴细胞和单核细胞介导的肿瘤细胞杀伤，而MRK17仅诱导淋巴细胞介导的ADCC反应。这些结果表明，IgG2a亚型的MRK16可能是一种有用的治疗剂，可通过ADCC反应根除表达P-糖蛋白的耐药癌细胞。
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