P-0097 Gemcitabine Monotherapy does not Impact Catumaxomab-Mediated Elimination of Epcam-Positive Tumor Cells in Vitro

Abstract

IntroductionThe trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) is approved in the EU for the intraperitoneal treatment of malignant ascites due to EpCAM-positive carcinomas. A functional immune system is essential for effective catumaxomab-mediated tumor cell elimination. Gemcitabine is a key drug utilized in all stages of treatment of pancreatic adenocarcinoma. Since gemcitabine may impair the functionality of immune cells required for catumaxomab's mode of action, this study investigated the potential influence of gemcitabine monotherapy on the cytotoxicity mediated by catumaxomab. MethodsPatients with pancreatic adenocarcinoma had received gemcitabine monotherapy as 1st-line treatment. Peripheral blood was collected at different time points before and during chemotherapy cycles and patient immune cells were used to assess catumaxomab-mediated cytotoxicity in vitro. Purified mononuclear cells (PBMC) were used to evaluate catumaxomab-mediated cytotoxicity in a co-culture test system with EpCAM-positive tumor target cells (HCT-8). 6 patients were included in the analyses (2-3 samples taken from each patient). ResultsEfficient killing of EpCAM-positive tumor cells was shown for all patient samples at catumaxomab concentrations that correspond to the clinical dose range. No negative impact of gemcitabine treatment on catumaxomab-mediated tumor cell killing was observed. ConclusionCatumaxomab induces efficient anti-tumor activity against epithelial tumor cells with immune cells from patients with pancreatic adenocarcinoma after gemcitabine treatment. These data provide a pharmacological basis for the possible integration of catumaxomab therapy into gemcitabine treatment regimens.