Cytokine Therapy By Allogenic Ifn-Alpha-Expressing Murine Colorectal Cancer Cells Suppresses Outgrowth Of Established Tumors In A Murine Hepatocellular Carcinoma Model

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Although several effective therapies for hepatocellular carcinoma (HCC) have been developed, many patients with both advanced cirrhosis and HCC are not able to receive those treatments because of their poor liver function. Thus, it is needed to establish a new effective therapy that has lesser side effects for those patients. We previously reported that immunotherapy by interferon-alpha (IFNa) and dendritic cells effectively suppressed outgrowth of established tumors and showed preventive effects in the murine colorectal cancer, MC38 cell model. We also revealed that tumor-specific cytotoxic T cell responses were important for these anti-tumor effects. In this study, we investigated the antitumor effect of allogenic cytokine (IFNa and IL-4)- expressing MC38 cells in the murine hepatocellular carcinoma, BNL model. There were no differences in cell growth between BNL cells and BNL cells co-incubated with cytokine-expressing MC38 cells in vitro. Balb/c mice were injected with 5x105 of BNL cells on their flank. Once BNL tumors were established, these mice received therapeutic injection of cytokine-expressing MC38 cells (2.5x105/mouse or 5x105/mouse) and tumor size was measured twice weekly. While tumor growth of the mice injected with MC38-IL4 was not suppressed (control; 421.0±146.9mm2, MC38-IL4 (5x105); 351.3±126.1mm2, p=0.33), injection of MC38-IFNa cells significantly suppressed the tumor growth by dose-dependent manner (MC38-IFNa: 5x105 cells; 183.5±46.2mm2, p=0.02). When we injected mice with both IFNa cells and IL-4 cells, any additive anti-tumor effects were not observed (mice injected both modified MC38: 5x105 cells each; 182±44.6 mm2, p=0.01). A BNL-specific cytolysis was detected when splenocytes of mice injected with MC38-IFNa were used as effector cells in a chromium-release assay. Furthermore, immunohistocemistrical analysis revealed that CD4+ T cells, CD8+ T cells and especially Gr-1+ cells infiltrated established BNL tumors of mice injected with MC38-IFNa. Our results suggest that the immunotherapy with allogenic IFNa-expressing cells has potent antitumor effects, and that it would be applicable for treatment to advanced HCC patients. 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 524. doi:1538-7445.AM2012-524