Abstract 4874: Interleukin-12/FasTI: A novel bi-functional fusion protein for cancer immunotherapy

Abstract

Abstract Whereas cancer immunotherapy with cytokines demonstrates effective in activating immune response against tumor cells, one major obstacle with the use of these cytokines is their severe side effects when delivered systemically at high doses. Another challenge is that advanced tumor cells often evade immunosurveillance of the immune system and block the Fas-mediated apoptosis by down-regulating its expression. In the present study, we report the design and preliminary evaluation of the antitumor activity of a novel fusion protein:mIL-12/FasTI, consisting of mIL-12 and the transmembrane and intracellular domains of Fas. The fusion construct (pmIL-12/FasTI) was transfected into mouse lung carcinoma cell line TC-1. Stable cell clones expressing the fusion protein were established as assayed by RT-PCR and immunohistochemistry. ELISA and cell proliferation analyses demonstrated that NK cells were effectively activated by the fusion protein with increased IFN-ã production and cytotoxicity. Enhanced caspase 3 activity of the clones when co-cultured with NK cells demonstrated that apoptosis was induced through Fas/FasL signaling pathway. The bifunctional protein is clearly more effective than IL-12 alone. It, therefore, represents a promising new therapeutic agent for cancer treatment when combined with tumor cell-specific gene delivery. Citation Format: Xi Yang, Ashlee Tietje, Xianzhong Yu, Yanzhang Wei. Interleukin-12/FasTI: A novel bi-functional fusion protein for cancer immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4874.