Injection of minute amounts of two immune-stimulating agents directly into solid tumors in mice was able to eliminate all traces of cancer, including distant untreated metastases, in approximately 90% of animals, according to a study published yesterday in Science Translational Medicine. The research was done by scientists at the Stanford University School of Medicine.
The method works by reactivating cancer-specific T cells previously inactivated by the cancer directly at the tumor site. One of the drugs works to amplify the expression of an activating receptor called OX40 on the surface of the T cells. The other drug, an antibody that binds to OX40, activates the T cells to target the cancer cells. The fact that the T cells are already found in the tumor means they recognize only cancer-specific proteins, eliminating off-target effects.
These tumor-specific T cells leave the original tumor to find and destroy other identical tumors throughout the body. In mice with transplanted mouse lymphoma tumors in two sites on their bodies injections of microgram amounts of treatment were able to eliminate tumors in 87 to 90 percent of the mice. Similar results were seen in mice bearing breast, colon and melanoma tumors. Mice engineered to spontaneously develop breast cancers also responded to treatment, with treatment of the first tumor often preventing the occurrence of future tumors and increasing lifespan.
When mice with two different types of tumors received treatment for one tumor, but not the other, only the treated tumor was affected, demonstrating the targeted nature of this tumor type.
"When we use these two agents together, we see the elimination of tumors all over the body," said Ronald Levy, MD, professor of oncology. "This approach bypasses the need to identify tumor-specific immune targets and doesn't require wholesale activation of the immune system or customization of a patient's immune cells."
Of the two agents, one is already approved for use in humans and the other has been tested for human use in several unrelated clinical trials. An upcoming clinical trial is expected to recruit about 15 patients with low-grade lymphoma to explore the combination treatment’s clinical applications.