TRION Research GmbH, Martinsried, Germany.
Cancer Res. 2012 Jan 1;72(1):24-32. doi: 10.1158/0008-5472.CAN-11-2235. Epub 2011 Nov 1.
Patients with malignant ascites secondary to primary carcinomas benefit from intraperitoneal therapy with the trifunctional antibody catumaxomab (anti-EpCAM × 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.
原发性癌继发恶性腹水患者从三功能抗体 catumaxomab（抗-EpCAM×抗-CD3）腹腔内治疗中获益。在这里，我们报告了对 258 例恶性腹水随机分为 catumaxomab 或对照组的患者的腹腔液样本进行分析，以研究 catumaxomab 治疗的分子作用。在 catumaxomab 组中，肿瘤细胞数量和腹腔中 VEGF 水平降低，而治疗后 CD4(+)和 CD8(+)T 细胞群体的激活状态增加了两倍以上。值得注意的是，CD133(+) / EpCAM(+)癌症干细胞从 catumaxomab 样本中消失，但从对照组样本中没有消失。体外研究表明，catu- maxomab 以一种与促炎 Th1 细胞因子释放相关的方式消除肿瘤细胞。总之，我们的研究结果表明，catu- maxomab 治疗激活了腹腔 T 细胞并消除了 EpCAM(+)肿瘤细胞，为理解免疫抑制性恶性腹水组织微环境中的体内疗效提供了分子和细胞基础。
