Abstract 4396: Combination of intratumoral regulated IL-12 gene delivery and systemic chemotherapy with Palifosfamide (IPM-Tris) enhances anti-tumor effects in breast cancer (4T1) model

A major obstacle for the development of effective immunotherapy is the ability of tumors to escape detection and/or destruction by the immune system. This study explored pairing a potent immunomodulatory cytokine (IL-12) with a bifunctional alkylating agent currently in Phase III clinical trials for soft tissue sarcoma (Palifosfamide, IPM-Tris). In this study intratumorally administered adenoviral vector, Ad-RTS-mIL-12, expressing IL-12 under the control of Rheoswitch Therapeutic System®, (RTS®), a novel inducible promoter system was used. Expression of IL-12 is regulated by oral administration of a small molecule activator ligand, INXN-1001 (AL). The in vitro transduction of the human fibrosarcoma cell line, HT1080, with Ad-RTS-hIL12 + AL at a MOI of 400 pfu, produced >6000-fold induction of human IL-12 above background, while IPM-Tris (1-3 uM) was cytotoxic in a variety of cancer cell lines. The effect of Ad-RTS-mIL12 + AL in combination with IPM-Tris was evaluated in a subcutaneous 4T1 syngeneic BALB/c mouse mammary tumor model at low doses, which were chosen to have minimal effect on tumor growth rate. Indeed, IPM-Tris alone (40 - 120 mg/m2) had little effect on tumor growth rate (< 30%) compared to vehicle. In contrast, a single intratumoral injection of Ad-RTS-mIL12 (1x1010 vp) and oral administration of AL (15, 30, 75 or 150 mg/m2) once daily for 5 days led to significant AL dose-related tumor growth inhibition (28, 29, 62, 59%, respectively; p 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 4396. doi:1538-7445.AM2012-4396