title: Immunomonitoring results of a phase II/III study of malignant ascites patients treated with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3).
abstract: 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.
authors: TRION Research GmbH, Martinsried, Germany. michael.jaeger@trionresearch.de
authors: Michael
authors: M
authors: Jäger
authors: Alexandra
authors: A
authors: Schoberth
authors: Peter
authors: P
authors: Ruf
authors: Juergen
authors: J
authors: Hess
authors: Michael
authors: M
authors: Hennig
authors: Barbara
authors: B
authors: Schmalfeldt
authors: Pauline
authors: P
authors: Wimberger
authors: Michael
authors: M
authors: Ströhlein
authors: Bettina
authors: B
authors: Theissen
authors: Markus M
authors: MM
authors: Heiss
authors: Horst
authors: H
authors: Lindhofer
mesh_terms: D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D001201:Ascites / Q000188:drug therapy* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008991:Monitoring, Physiologic / Q000379:methods
chemical_list: D018033:Antibodies, Bispecific; C522419:catumaxomab