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卡妥索单抗对卵巢癌骨髓和血液中肿瘤细胞的影响。

Influence of catumaxomab on tumor cells in bone marrow and blood in ovarian cancer.

作者信息

Wimberger P, Heubner M, Lindhofer H, Jäger M, Kimmig R, Kasimir-Bauer S

机构信息

Department of Gynecology and Obstetrics, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.

出版信息

Anticancer Res. 2009 May;29(5):1787-91.

Abstract

The trifunctional antibody catumaxomab with bispecificity for the epithelial cell adhesion molecule EpCAM and the T-cell antigen CD3, is a new therapeutic strategy for ovarian cancer patients with symptomatic malignant ascites. Whether or not intraperitoneal (i.p.) catumaxomab-therapy has influence on disseminated and circulating tumor cells was investigated by analyzing cytokeratin-positive (CK+) cells in bone marrow (BM) and peripheral blood (PB). Fourteen ovarian cancer patients with symptomatic ascites were treated with catumaxomab (up to 5 i.p.-infusions; increasing dosages (10-200 microg)). CK+-cells were isolated before and after antibody-therapy by density gradient centrifugation and immunocytochemistry (anti-CK antibody A45-B/B3). Catumaxomab-treatment resulted in the sustained reduction of ascites flow and arrested ascites reaccumulation. The mean overall survival was 8 months. CK+-cells in the BM were found in 70% before and 83% after therapy (in the PB 57% and 42%, respectively). A marked reduction of CK+-cells occurred in the BM in 2 and in the PB in 4 patients. Catumaxomab shows a strong intraperitoneal effect and possibly also systemic effects on tumor cells in the BM and PB.

摘要

三功能抗体卡妥索单抗对上皮细胞黏附分子EpCAM和T细胞抗原CD3具有双特异性,是治疗有症状恶性腹水的卵巢癌患者的一种新治疗策略。通过分析骨髓(BM)和外周血(PB)中的细胞角蛋白阳性(CK+)细胞,研究腹腔内(i.p.)注射卡妥索单抗治疗是否对播散性和循环肿瘤细胞有影响。14例有症状腹水的卵巢癌患者接受了卡妥索单抗治疗(最多5次腹腔内输注;剂量递增(10 - 200微克))。在抗体治疗前后,通过密度梯度离心和免疫细胞化学(抗CK抗体A45 - B/B3)分离CK+细胞。卡妥索单抗治疗导致腹水流量持续减少并阻止腹水再次积聚。平均总生存期为8个月。治疗前70%的患者骨髓中发现CK+细胞,治疗后为83%(外周血中分别为57%和42%)。2例患者骨髓中CK+细胞显著减少,4例患者外周血中CK+细胞显著减少。卡妥索单抗对骨髓和外周血中的肿瘤细胞显示出强大的腹腔内效应,可能还有全身效应。

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