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【Blood】CD137刺激增强抗CD20抗体的抗淋巴瘤活性
CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies.
Kohrt HE, Houot R, Goldstein MJ, Weiskopf K, Alizadeh AA, Brody J, Müller A, Pachynski R, Czerwinski D, Coutre S, Chao MP, Chen L, Tedder TF, Levy R.
Department of Medicine, Division of Oncology, Stanford University, Stanford, CA;
Abstract
Antibody-dependent cell-mediated cytotoxicity (ADCC), which is largely mediated by natural killer (NK) cells, is thought to play an important role in the efficacy of rituximab, an anti-CD20 monoclonal antibody (mAb) used to treat patients with B-cell lymphomas. CD137 is a costimulatory molecule expressed on a variety of immune cells after activation, including NK cells. In the present study, we show that an anti-CD137 agonistic mAb enhances the antilymphoma activity of rituximab by enhancing ADCC. Human NK cells up-regulate CD137 after encountering rituximab-coated tumor B cells, and subsequent stimulation of these NK cells with anti-CD137 mAb enhances rituximab-dependent cytotoxicity against the lymphoma cells. In a syngeneic murine lymphoma model and in a xenotransplanted human lymphoma model, sequential administration of anti-CD20 mAb followed by anti-CD137 mAb had potent antilymphoma activity in vivo. These results support a novel, sequential antibody approach against B-cell malignancies by targeting first the tumor and then the host immune system.
PMID: 21193697 [PubMed - in process] CD137刺激增强抗CD20抗体的抗淋巴瘤活性。
NK细胞介导的抗体依赖性细胞介导细胞毒作用（ADCC）在利妥昔治疗B细胞淋巴瘤的疗效中有着重要的作用。CD137是多种免疫细胞（包括NK细胞）活化后表达的共刺激分子。本研究中，我们发现抗CD137单抗通过增强ADCC增强利妥昔抗肿瘤的活性，利妥昔结合的肿瘤B细胞可以使NK细胞上调CD137，继而刺激这些有抗CD137单抗作用的NK细胞增强利妥昔依赖的抗肿瘤细胞的细胞毒性。在同系的鼠淋巴瘤模型和模拟移植人淋巴瘤模型，CD20单抗后使用CD137单抗序贯治疗在体内有很强的抗肿瘤效果。这些结果提示一种新的抗体序贯治疗方法即先靶定肿瘤然后靶定宿主免疫系统。 《世界最新癌讯》第廿四辑〈二七年九月〉癌症的发病机制一向为人关注.最近,中国科学院上海生命科学研究院营养科学研究所的一... 《临床肿瘤学杂志(J Clin Oncol)》上. 患者被给予标记了示踪物的抗 CD20抗体托西莫...www.taishan-international.org/-2007-02-15-快照-[标签:content2]
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作者:admin@医学,生命科学 2011-03-05 00:17
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