IL-24

Innovation: Therapeutics & drug delivery—Cancer Terminator Viruses for the targeted therapy of a diverse array of aggressive tumor types
Targeted Cancer(s): Glioblastoma & melanoma
Scientific Leadership: Paul B. Fisher, M.Ph., Ph.D.; Webster Cavenee, Ph.D.
Stage of Project: Approved matching funds from Virginia Catalyst for Phase I clinical trials

Cancer Terminator Viruses (CTV) have been engineered which are capable of producing multiple types of cytokines (a type of protein), including IL-24 (mda-7), an interleukin, and its next generation “Superkine,” which can destabilize and kill cancer cells. In development are CTV therapeutic candidates which work by secreting proteins that can locate and destroy tumors in all parts of the body by directly promoting programmed and immunogenic cell death, inhibiting new blood vessel formation (known as angiogenesis) and sensitizing tumor cells to conventional therapies (including radiation, chemotherapy and immunotherapy), without inducing toxicity in normal cells or tissues.

These interleukins can be administered through vector mediation, cellular delivery or as pure therapeutic proteins. Furthermore, an innovative method, ultrasound-targeted microbubble-destruction, can be employed to deliver the drug directly to tumors or the tumor microenvironment. Additionally, the efficacy of the cytokines against primary and metastatic tumors can be enhanced further by combining them with radiation, chemotherapy or rationally-designed anti-cancer targeted drugs.

• It is estimated that nearly 90% of patients with advanced cancers die as a result of complications associated with tumor cell invasion into normal tissue and metastatic spread from primary tumor sites to secondary locations in the body.
• Glioblastoma, the first disease being targeted, is the most common and aggressive type of brain cancer and its prognosis is extremely poor, with median overall survival at approximately 15 months and the average five-year survival rate less than 5%.

• Targeting cancer cells with selectively replicating viruses to cause cancer cells to produce and secrete IL-24 and create a broader field effect should impact primary site tumors and more distant tumors. In experiments, this has led to longer survival, even with subjects that have distant metastases.
• Since IL-24 can be delivered in a variety of ways, broad applicability is likely. Experimental data are in hand showing efficacy of IL-24 in cancers, including glioblastoma, melanoma and carcinomas of the breast, colon, lung, bladder, liver, pancreas and prostate.
• Combining IL-24 with other drugs that target specific molecular pathways in cancer cells can improve its effectiveness.

• Potency and Duration of Action: Potent anti-cancer and anti-metastatic effects of IL-24 in several animal models promoting long-term survival
• Proof of Concept: IL-24 is efficacious in several rodent models of glioblastoma and other cancers
• Safety and Tolerability: Given that the early version of IL-24 has been administered to patients and has shown no adverse events and displays clinical efficacy, it is believed to be unlikely that any issues will be uncovered in Phase 1 clinical testing of the newer Superkine
• Clinical Development Plan: The initial clinical trial will test safety in glioblastoma patients treated with IL-24-CTV