Yesterday, cancer therapy-focused biopharmaceutical company ZIOPHARM Oncology announced the presentation of results from a study in a breast cancer murine model. The study demonstrated the anti-tumor effects and tolerability of Ad-RTS-mIL-12, which is a viral vector DNA-based therapeutic for the controlled, local expression of IL-12 – an important protein for enhancing antitumor immunity. The data was presented at the American Association for Cancer Research 2013 Annual Meeting, taking place in Washington, D.C., April 6-10. The study was jointly conducted by Intrexon Corporation and ZIOPHARM, which is Intrexon’s exclusive channel partner for the development of in vivo oncology therapeutics.
During the study, intratumoral administration of Ad-RTS-mIL-12 (Ad) was examined in a 4T1 BALB/c mouse breast carcinoma model. The production of murine IL-12 was controlled using Intrexon’s RheoSwitch Therapeutic System (RTS) platform along with oral administration of the activator ligand INXN-1001 (AL), which was found to elicit a dose-related increase in plasma AL levels, which correlated with increasing tumor AL levels. The tumor AL level increase in combination with Ad, in turn, resulted in a dose-related increase in expression of mIL-12 in the tumor, with a minimal increase in serum mIL-12.
The increase in AL-regulated tumor IL-12 levels correlated with an increase in tumor-infiltrating CD4+ and CD8+ T cells in and adjacent to the tumor, concomitant with a decrease in tumor regulatory T cells. The result was a dose-related tumor growth rate decrease. The therapeutic strategy, moreover, seems to be well-tolerated, as no change was observed in clinical signs or body weight in the treated animals when compared with vehicle alone.
Two of the major obstacles in developing immunotherapeutics for the treatment of cancer are the ability of tumors to evade the immune system’s anti-cancer capabilities and also the toxicity commonly associated with the systemic administration of immunomodulating agents. In order to overcome these challenges, Ad-RTS-IL-12 has been developed, which is a DNA-based system for the regulated expression of IL-12, allowing for localized, controlled expression of immunomodulating cytokines and activation of their corresponding anti-tumor effects. Now, this strategy is being clinically tested with the recent launch of a Phase 2 study of Ad-RTS-IL-12 combined with palifosfamide for treating advanced breast cancer.
“These results support the hypothesis that localized delivery of IL-12 results in an increase in tumor infiltrating lymphocytes concomitant with a reduction in tumor growth,” said ZIOPHARM CEO Jonathan Lewis, M.D., Ph.D. “These findings suggest the applicability of this strategy in the treatment of breast cancer – especially in the context of recent literature addressing the positive correlation of survival with immune response measured in breast cancer tumors treated with non-immune therapies. This novel synthetic biology approach, which is being explored in several ongoing clinical studies, holds transformative potential for the treatment of cancer.”
ZIOPHARM Oncology is a biopharmaceutical company focused on developing and commercializing new cancer therapies. The company’s operations are located in Boston, Mass., and New York City. For more information, visit www.ziopharm.com
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