Small Molecule STING Agonists for Glioma Immunotherapy
Glioma, a common and deadly brain tumor in humans and dogs, remains especially difficult to treat using conventional therapies due to its tendency to grow deep within the brain and infiltrate into surrounding structures. It's well-accepted that the body’s own immune system is capable of slowing the growth of, and even of destroying, tumor cells. However, the immune system of the brain is difficult to stimulate due to the protective barrier between the bloodstream and the brain.
Recently, new therapies to treat glioma have focused on activating the immune system of the brain to fight the tumors. One general activating molecule that is known to be important in regulating the growth of glioma is STING (stimulator of interferon genes). STING is normally stimulated by the presence of bacterial DNA, and it, in turn, increases the production of local signals that increase tumor-fighting immune cell activity.
Our trial drug, IACS-8803, is a small molecule that mimics the structure of the bacterial DNA and activates STING. We inject it directly into the tumor using computer-guided instruments to minimize the impact of the drug on the healthy surrounding brain tissue. The drug remains within the brain, so it should also have minimal impact on the rest of the body.
We know that this drug can reduce the growth of gliomas in mice in the lab, that it generates an immune response in the brains of dogs with gliomas, and that it can be given safely under the skin in healthy dogs at much higher doses than are used in our trial. Because the skin is much more immune-reactive than the brain, this likely means it can be given safely in the brain, too.
Eligibility:
- Dogs that are candidates for our trial must have had a high-grade glioma diagnosed based on a recent MRI.
- Dogs may have had other, previous treatments for the tumor, such as radiation therapy or surgical resection.
During the trial:
- After consultation and enrollment, dogs would have two injections into their tumor (4-6 weeks apart) performed at Texas A&M and would need to return to A&M regularly over the next 6 months for checkups and brief repeat MRIs to track changes in the size of the tumor.
- Dogs in the trial may also take any medications prescribed to control seizures and standard medications given to control swelling around brain tumors (e.g., prednisone). During participation in the trial, dogs may not have radiation therapy, surgery, or other chemotherapy to treat the brain tumor.
Financial Obligations:
All costs associated with anesthesia and equipment for the injections, hospitalization, recheck visits, and MRIs will be covered by the study.
Disclaimers:
- Serious complications may result from intracranial injections, which must be performed under general anesthesia. Although these complications are rare, they include worsening neurological function, seizures, life-threatening bleeding, and even death.
- At this time, we do not know if receiving the drug will slow the growth of gliomas in dogs’ brains.
For more information about this trial:
- Please ask your veterinary neurologist or contact us at the Texas A&M Small Animal Hospital.
- This trial is being administered by Dr. Jon Levine and Dr. Beth Boudreau, both veterinary neurologists at Texas A&M.
- We can be reached at 979-845-2351 or by e-mail at jlevine@cvm.tamu.edu or bboudreau@cvm.tamu.edu.
