Effect of catumaxomab on EpCAM+ tumor cells in vitro in the presence of immune effector cells from ovarian cancer patients treated with chemotherapy.

Abstract

e13043 Background: The trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) is approved in the EU for the intraperitoneal treatment of malignant ascites. Since chemotherapy may impair the functionality of immune cells required for catumaxomab’s mode of action, this study investigated the potential influence of chemotherapy treatment of patients with ovarian cancer on the anti-tumor activity of catumaxomab. Methods: Immune cells of patients taken at different time points before/after chemotherapy treatment were used to assess catumaxomab-mediated cytotoxicity in vitro. A total of 22 ovarian cancer patients were selected for the analysis. Patients had received carboplatin/paclitaxel (1st-line treatment) or topotecan or doxorubicin monotherapy as 2nd–x-line treatment, respectively. Peripheral blood was collected and purified patient PBMCs were used as effector cells to determine catumaxomab-mediated cytotoxicity in a co-culture test system with SK-OV-3 ovarian tumor cells as EpCAM+ target cells. Results: No significant interference of chemotherapeutic treatment on catumaxomab-mediated tumor cell killing was observed. Activity in vitro varied when comparing patient’s immune cells to healthy control PBMCs. However, for all patient samples efficient elimination of tumor cells was demonstrated at catumaxomab concentrations that correspond to the therapeutic dose range. Conclusions: Catumaxomab induces a potent destruction of EpCAM+ tumor cells with immune effector cells from ovarian cancer patients treated with chemotherapy. Thus, these nonclinical data provide a pharmacological basis for the integration of catumaxomab therapy into chemotherapeutic regimens.