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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Immunomonitoring results of a phase II/III study of malignant ascites patients treated with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3). / Jäger, Michael; Schoberth, Alexandra; Ruf, Peter; Hess, Juergen; Hennig, Michael; Schmalfeldt, Barbara; Wimberger, Pauline; Ströhlein, Michael; Theissen, Bettina; Heiss, Markus M; Lindhofer, Horst.
in: CANCER RES, Jahrgang 72, Nr. 1, 01.01.2012, S. 24-32.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Immunomonitoring results of a phase II/III study of malignant ascites patients treated with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3)
AU - Jäger, Michael
AU - Schoberth, Alexandra
AU - Ruf, Peter
AU - Hess, Juergen
AU - Hennig, Michael
AU - Schmalfeldt, Barbara
AU - Wimberger, Pauline
AU - Ströhlein, Michael
AU - Theissen, Bettina
AU - Heiss, Markus M
AU - Lindhofer, Horst
N1 - ©2011 AACR.
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
KW - Antibodies, Bispecific
KW - Ascites
KW - CD4-Positive T-Lymphocytes
KW - CD8-Positive T-Lymphocytes
KW - Humans
KW - Lymphocyte Activation
KW - Monitoring, Physiologic
U2 - 10.1158/0008-5472.CAN-11-2235
DO - 10.1158/0008-5472.CAN-11-2235
M3 - SCORING: Journal article
C2 - 22044753
VL - 72
SP - 24
EP - 32
JO - CANCER RES
JF - CANCER RES
SN - 0008-5472
IS - 1
ER -
