Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30
Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30
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DOI：
10.1182/blood-2007-06-097014
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发表时间：
2007-12-15
期刊：
影响因子：
20.3
通讯作者：
Gerber, Hans-Peter
中科院分区：
文献类型：
--
作者：
Oflazoglu, Ezogelin;Stone, Ivan J.;Gerber, Hans-Peter
CD30表达增加与多种血液系统恶性肿瘤相关，包括霍奇金病（HD）和间变性大细胞淋巴瘤（ALCL）。抗CD30单克隆抗体SGN - 30通过促进CD30（+）肿瘤细胞的生长停滞和DNA断裂诱导直接的抗肿瘤活性。在本研究中，我们探讨了Fc介导的效应细胞功能对SGN - 30活性的作用。我们确定由巨噬细胞介导的抗体依赖的细胞吞噬作用在体外对肿瘤活性有显著贡献。为了明确体内介导抗肿瘤活性的宿主效应细胞的特性，我们研究了在霍奇金病播散模型（L540cy）中效应细胞消融的影响。巨噬细胞的耗竭显著降低了SGN - 30的疗效，表明在该模型中巨噬细胞对SGN - 30的疗效有显著贡献。这些发现可能对在霍奇金病和间变性大细胞淋巴瘤中使用SGN - 30进行的临床试验中的患者分层或联合治疗策略具有影响。
Increased expression of CD30 is associated with a variety of hematologic malignancies, including Hodgkin disease (HD) and anaplastic large cell lymphoma (ALCL). The anti-CD30 monoclonal antibody SGN-30 induces direct antitumor activity by promoting growth arrest and DNA fragmentation of CD30(+) tumor cells. In this study, we investigated the contributions of Fc-mediated effector cell functions to SGN-30 activity. We determined that antibody-dependent cellular phagocytosis, mediated by macrophages, to contribute significantly to antitumor activity in vitro. To delineate the identity of the host effector cells involved in mediating antitumor activity in vivo, we studied the effects of effector cell ablation in a disseminated model of HD (L540cy). Depletion of macrophages markedly reduced efficacy of SGN-30, demonstrating that macrophages contribute significantly to SGN-30 efficacy in this model. These findings may have implications for patient stratification or combination treatment strategies in clinical trials conducted with SGN-30 in HD and ALCL.