Abstract 3211: MTL-CEBPA combined with radiofrequency ablation and immunotherapy enhances immunological anti-tumour response in an HCC mouse model

Abstract

Abstract The transcription factor CEBPA (CCAAT/enhancer-binding protein alpha) is recognised for its antiproliferative effects. MTL-CEBPA is a small activating RNA drug which upregulates gene expression of CEBPA and amongst other effects causes and immunomodulatory effect on peripheral granulocytes. Radiofrequency ablation (RFA) is standard treatment for some tumour types such as liver cancer and induces modulation of both innate and adaptive immune systems. To investigate any synergistic effect of MTL-CEBPA with RFA and immune checkpoint inhibition we initiated a reverse translation experiment, where syngeneic BNL hepatocellular carcinoma tumour cells were injected in the two opposite flanks of immunocompetent BALB/c mice (n=8 in each group). Treatments for hepatoma bearing mice included: 1) RFA on one flank (day 0), 2) Anti-PD-1 inhibition immunotherapy (RMP1-14 antibody, BioXCell, West Lebanon, NH, USA at 200 μg IV/mouse/dose on days 0, 2 & 5) and 3) MTL-CEBPA (3mg/kg IV/mouse/dose on days 0, 2 & 5) as well as combinations of all 3 interventions. We found that tumour control on the opposite flank was augmented by addition of RFA and most significant in the triple combination group (RFA + anti-PD1 + MTL-CEBPA) in which 2/8 animals showed a complete response and 5/8 a partial response. This was also the only group that showed a statistically significant increase in CD8+ (Cytotoxic) as well as CD49b+/CD45+ (Natural Killer) tumour infiltrating lymphocytes. These data suggest a clinical role for combination treatment with checkpoint blockade, RFA and MTL-CEBPA through synergistic priming of the immune tumour response, enabling RFA to have a pronounced anti-tumour abscopal effect. Citation Format: Mikael H. Sodergren, Kai-Wen Huang, Vikash Reebye, Cheng-Ean Chee, Dimitris Zacharoulis, Robert Habib, David Blakey, John Rossi, Nagy Habib. MTL-CEBPA combined with radiofrequency ablation and immunotherapy enhances immunological anti-tumour response in an HCC mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3211.