Abstract 2829: Activity of EP-100 in Non-Hodgkin's Lymphoma - synergy in combination

EP-100 is a targeted anti-cancer peptide comprised of Luteinizing Hormone Releasing Hormone (LHRH) fused to a membrane-disrupting peptide (MDP). It is currently in Phase 1 clinical trial in tumors that over-express LHRH receptors. EP-100 kills cancer cells directly via membrane disruption. We tested a combination of EP-100 and doxorubicin in multi-drug resistant Non-Hodgkin9s Lymphoma (NHL) cell lines and primary cells from refractory/relapsed NHL patients. Cells were cultured in the presence of EP-100 (0.00001-100 μM) or unconjugated MDP alone or in combination with doxorubicin (0.0000056 - 56.5 µM) and EP 100 at 0.5, 5, 50 and 500 nM. Cytotoxicity was determined by membrane integrity and cell viability assays. LHRH receptor expression was determined by flow cytometry. The effect of EP-100 on purified human recombinant p-glycoprotein (h-pgp) pump was measured by ATPase activity. The IC 50 values [µM] for EP-100 alone were 0.52±0.13, 0.95±0.2, 2.8±0.5, 0.9±0.13 and values for unconjugated MDP were 59±1.5, 25.6±1.7, 6.1±0.8 after 5 h of incubation for Daudi, Raji, Toledo, Hut78 cells, respectively. EP-100 specifically killed NHL patient cells and unconjugated MDP was ineffective. The IC 50 values for EP-100 were 1.2 ± 0.1µM for cells obtained from three Mantle Cell Lymphoma patients (N=3), 2.3± 0.1 µM for Diffuse Large B Cell Lymphoma patient (N=1), 1.7± 0.3 µM for Follicular Lymphoma patients (N=4), and 1.6 ± 0.1 µM for one Waldenstr[[Unable to Display Character: ő]]m Macroglobunemia patient. EP-100 or unconjugated MDP did not kill B-cells from normal subjects (N=2) after 5 hour incubation. LHRH receptors were over-expressed on cell lines and patient cells. Combination of EP-100 with doxorubicin resulted in synergistic responses after 72 hours of incubation and Combination Index was Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2829. doi:1538-7445.AM2012-2829