472P - Catumaxomab shows comparable anti-tumor activity in vitro with immune effector cells from different ethnicities with different FcγR gene polymorphi...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Drug Development
Presenter Frederik Marmé
Authors F. Marmé1, K. Hasegawa2, H. Martinius3, J. Atz3, K. Fujiwara2
  • 1Inf 460, Universitätsfrauenklinik Heidelberg & Nationales Centrum für Tumorerkrankungen (NCT), 69120 - Heidelberg/DE
  • 2Department Of Gynecologic Oncology, Saitama International Medical Center, Saitama/JP
  • 3Munich, Fresenius Biotech GmbH, Munich/DE

Abstract

Background

Catumaxomab, the approved therapy for treatment of malignant ascites, exerts its anti-tumor effects via T-cell-mediated lysis, antibody-dependent cell-mediated cytotoxicity, and phagocytosis via activation of FcγR-positive accessory cells. It has been reported that FcγR-polymorphisms influence the IgG binding capacity of the receptor and that ethnic groups may differ with respect to responsiveness of immune effector cells to antibody-based therapies. The present nonclinical study therefore investigated potential inter-ethnic differences (Caucasian vs. Japanese, Korean, Black African and Hispanic Donors) and FcγR-gene polymorphisms with regard to the potency of catumaxomab in vitro.

Methods

Blood samples of healthy subjects of different ethnic background (25 donors of Caucasian, Korean, Black African and Hispanic ethnicity and 15 Japanese donors) were collected for comparative analyses. PBMCs were purified from whole blood samples and used as effector cells evaluating catumaxomab-mediated cytotoxicity towards EpCAM+ tumor target cells (HCT-8; colon) in vitro. Furthermore, the samples were genotyped for FcγR IIa and FcγR IIIa gene polymorphisms by PCR.

Results

The comparative analysis of catumaxomab-mediated cytotoxicity obtained for the individual ethnic subgroups did not reveal major inter-ethnic differences although genetic polymorphisms for FcγR IIa/IIIa had been identified among donors. Even though a wider variability was observed among Caucasians, the potency range observed with immune effector cells of Japanese, Korean, Black African and Hispanic was found to be within the potency range observed for the Caucasian ethnicity.

Conclusions

No impact of ethnic background or FcγRIIa/IIIa polymorphism on the immune cell-mediated pharmacological activity of the trifunctional antibody catumaxomab could be identified in vitro. Therefore, it can be assumed that patients with a different ethnic background may also benefit from catumaxomab therapy as already demonstrated for Caucasian patients.

Disclosure

F. Marmé: consultant for Fresenius Biotech GmbH.

K. Hasegawa: financial support for clinical studies from Fresenius Biotech GmbH.

H. Martinius: works for Fresenius Biotech GmbH.

J. Atz: works for Fresenius Biotech GmbH.

K. Fujiwara: financial support for clinical studies from Fresenius Biotech GmbH.