Immunomonitoring Results of a Phase II/III Study of Malignant Ascites Patients Treated with the Trifunctional Antibody Catumaxomab (Anti-EpCAM x Anti-CD3)
Immunomonitoring Results of a Phase II/III Study of Malignant Ascites Patients Treated with the Trifunctional Antibody Catumaxomab (Anti-EpCAM x Anti-CD3)
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DOI：
10.1158/0008-5472.can-11-2235
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发表时间：
2012-01-01
期刊：
影响因子：
11.2
通讯作者：
Lindhofer, Horst
中科院分区：
文献类型：
--
作者：
Jaeger, Michael;Schoberth, Alexandra;Lindhofer, Horst
原发癌继发恶性腹水的患者受益于三功能抗体Catumaxomab(抗EpCAM x抗CD3)的腹膜内治疗。在这里，我们报告了对258例恶性腹水患者腹腔液样本的分析，这些患者随机分为Catumaxomab组和对照组，以研究Catumaxomab治疗的分子效应。在Catumaxomab组，治疗后肿瘤细胞数量和腹膜血管内皮生长因子水平下降，而CD4(+)和CD8(+)T细胞群的激活状态增加了两倍多。值得注意的是，CD133(+)/EpCAM(+)癌症干细胞从Catumaxomab样本中消失，但没有从对照样本中消失。体外研究表明，Catumaxomab通过释放促炎Th1细胞因子来消除肿瘤细胞。总之，我们的研究结果表明，Catumaxomab治疗激活了腹膜T细胞，消除了EpCAM(+)肿瘤细胞，为了解免疫抑制的恶性腹水组织微环境中的体内疗效奠定了分子和细胞基础。巨蟹座；72(1)；24-32。(C)2011年AACR。
Patients with malignant ascites secondary to primary carcinomas benefit from intraperitoneal therapy with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3). Here, we report the analysis of peritoneal fluid samples from 258 patients with malignant ascites randomized to catumaxomab or control groups to investigate the molecular effects of catumaxomab treatment. In the catumaxomab group, tumor cell numbers and peritoneal levels of VEGF decreased, whereas the activation status of CD4(+) and CD8(+) T-cell populations increased more than two-fold after treatment. Notably, CD133(+)/EpCAM(+) cancer stem cells vanished from the catumaxomab samples but not from the control samples. In vitro investigations indicated that catumaxomab eliminated tumor cells in a manner associated with release of proinflammatory Th1 cytokines. Together, our findings show that catumaxomab therapy activates peritoneal T cells and eliminates EpCAM(+) tumor cells, establishing a molecular and cellular basis to understand in vivo efficacy within the immunosuppressed malignant ascites tissue microenvironment. Cancer Res; 72(1); 24-32. (C) 2011 AACR.