Turn cold tumors hot
Ziopharm’s Controlled IL-12 platform can help provide therapy for cold tumors—ones that exhibit little or no immune system activity— by turning them hot by calling in an immune response. We are developing IL-12 as a monotherapy and in combination with checkpoint inhibitors to treat brain cancer and are exploring its therapeutic potential in other solid tumors, as well.
- 1. IL-12 coded within replication incompetent adenovirus (Ad) delivered to tumor site
- 2. Patient takes a capsule, veledimex, which turns on the IL-12 production
- 3. IL-12 signals killer T cells to migrate to tumor site and begin a sustained attack
“A cold tumor is an immunological desert. It has no T cells to fight against the cancer cells. A hot tumor is loaded with T cells.”
What it is
IL-12 is a powerful cytokine and master regulator of the immune system. Ad-RTS-hIL-12 plus veledimex is a gene therapy with an Adenoviral vector (Ad) providing the vehicle engineered to express IL-12 under the control of the RheoSwitch Therapeutic System® (RTS®).
How it works
Our Controlled IL-12 platform turns on expression of IL-12 on demand. IL-12 acts as a warning beacon to attract immune cells, signaling for T cells to attack and destroy cancerous tissue. Genes coded to produce IL-12 are first delivered to tumor sites and then patients take a capsule called veledimex which triggers the implanted genes to produce IL-12 to varying degrees, depending on dosage. In this way, we can increase or decrease expression levels of IL-12 or turn it off altogether.
How patients benefit
Our team has conducted clinical trials of our Controlled IL-12 platform in more than 80 patients with glioblastoma, breast cancer, and melanoma. Our data has shown that Controlled IL-12 drives T cells deep within a tumor for weeks to months at a time with extensive infiltration of activated CD8+ T cells and interferon gamma and upregulation of PD-1 and PD-L1 levels. Tumor samples taken from patients treated with Ad-RTS-hIL-12 plus veledimex show evidence of both the immune system attacking the cancer cells as well as the cancer trying to defend itself. MRI evidence shows tumor sites shrinking, and most importantly, we have seen improvements in median overall survival for patients with recurrent glioblastoma. See details of what Ziopharm presented at the 2017 annual meeting of the Society of Neurologic Oncology.
Potential for combination therapy
Controlled IL-12 has shown it can recruit killer T cells into the tumor and increase expression of checkpoints in the tumor microenvironment. Combining it with checkpoint inhibitors has the potential to further improve anti-cancer effects and provide a new therapeutic option for cancer.
Advancing in the clinic
We currently have open trials evaluating Ad-RTS-hIl-12 plus veledimex as a monotherapy to treat patients with recurrent glioblastoma and in combination with an anti-PD1 checkpoint inhibitor to treat patients with recurrent glioblastoma, and we are exploring additional tumor types.