Lubeck M D, Kimoto Y, Steplewski Z, Koprowski H
Wyeth Laboratories, Philadelphia, Pennsylvania 19101.
Cell Immunol. 1988 Jan;111(1):107-17. doi: 10.1016/0008-8749(88)90055-x.
We evaluated the capacity of freshly isolated blood monocytes to mediate antibody-dependent cellular-mediated cytotoxicity (ADCC) in cooperation with murine anti-tumor monoclonal antibodies (MAbs). Blood monocytes isolated from most donors by adherence selection to fibronectin-coated plastic surfaces and subsequently depleted of natural killer/killer (NK/K) cells exhibited significant ADCC activity against tumor cell lines in combination with an IgG3 antitumor MAb (BR55-2). However, significant variation in ADCC competence was observed among donors. Culture parameters influencing monocyte ADCC activity were evaluated and optimized. The influence of MAb isotype on ADCC capacity of anti-tumor MAbs was also evaluated using anti-tumor class-switch variant hybridoma proteins and a panel of anti-tumor MAbs. MAbs of the IgG2a and IgG3 subclasses exhibited high ADCC potential, whereas MAbs of the IgG2b subclass exhibited no ADCC activity. One of two IgG1 MAbs tested exhibited high ADCC activity with monocyte effectors. The role of monocytes or macrophages in tumor remission of cancer patients undergoing MAb immunotherapy is not known. However, correlative studies of monocyte ADCC capacity and responsiveness of cancer patients to MAb immunotherapy may help to establish the role of these effectors in MAb-mediated tumor remissions.
我们评估了新鲜分离的血液单核细胞与鼠抗肿瘤单克隆抗体（MAb）协同介导抗体依赖性细胞介导的细胞毒性（ADCC）的能力。通过在纤连蛋白包被的塑料表面进行黏附选择从大多数供体中分离出的血液单核细胞，随后去除自然杀伤/杀伤（NK/K）细胞，与IgG3抗肿瘤MAb（BR55-2）联合时，对肿瘤细胞系表现出显著的ADCC活性。然而，在供体之间观察到ADCC能力存在显著差异。对影响单核细胞ADCC活性的培养参数进行了评估和优化。还使用抗肿瘤类别转换变体杂交瘤蛋白和一组抗肿瘤MAb评估了MAb同种型对抗肿瘤MAb的ADCC能力的影响。IgG2a和IgG3亚类的MAb表现出高ADCC潜力，而IgG2b亚类的MAb则未表现出ADCC活性。所测试的两种IgG1 MAb中的一种与单核细胞效应器表现出高ADCC活性。单核细胞或巨噬细胞在接受MAb免疫治疗的癌症患者肿瘤缓解中的作用尚不清楚。然而，对癌症患者单核细胞ADCC能力和对MAb免疫治疗反应性的相关性研究可能有助于确定这些效应器在MAb介导的肿瘤缓解中的作用。
