Injecting minute amounts of two immune-stimulating agents directly into solid tumours in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases, according to a study by researchers at the Stanford University School of Medicine. The approach works for many different types of cancers, including those that arise spontaneously, the study found.
The researchers believe the local application of very small amounts of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with bodywide immune stimulation.
“When we use these two agents together, we see the elimination of tumours all over the body,” said Ronald Levy, MD, professor of oncology. “This approach bypasses the need to identify tumour-specific immune targets and doesn’t require wholesale activation of the immune system or customisation of a patient’s immune cells.”
One agent is currently already approved for use in humans; the other has been tested for human use in several unrelated clinical trials. A clinical trial was launched in January to test the effect of the treatment in patients with lymphoma.
Levy, who holds the Robert K. and Helen K. Summy Professorship in the School of Medicine, is the senior author of the study, which was published Jan. 31 in Science Translational Medicine. Instructor of medicine Idit Sagiv-Barfi, PhD, is the lead author.
Levy is a pioneer in the field of cancer immunotherapy, in which researchers try to harness the immune system to combat cancer. Research in his laboratory led to the development of rituximab, one of the first monoclonal antibodies approved for use as an anticancer treatment in humans.
Some immunotherapy approaches rely on stimulating the immune system throughout the body. Others target naturally occurring checkpoints that limit the anti-cancer activity of immune cells.
Still others, like the CAR T-cell therapy recently approved to treat some types of leukemia and lymphomas, require a patient’s immune cells to be removed from the body and genetically engineered to attack the tumour cells.
Many of these approaches have been successful, but they each have downsides — from difficult-to-handle side effects to high-cost and lengthy preparation or treatment times.
“All of these immunotherapy advances are changing medical practice,” Levy said. “Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumour itself. In the mice, we saw amazing, bodywide effects, including the elimination of tumours all over the animal.”
Cancers often exist in a strange kind of limbo with regard to the immune system. Immune cells like T cells recognise the abnormal proteins often present on cancer cells and infiltrate to attack the tumour. However, as the tumour grows, it often devises ways to suppress the activity of the T cells.
Levy’s method works to reactivate the cancer-specific T cells by injecting microgram amounts of two agents directly into the tumour site. (A microgram is one-millionth of a gram). One, a short stretch of DNA called a CpG oligonucleotide, works with other nearby immune cells to amplify the expression of an activating receptor called OX40 on the surface of the T cells.
The other, an antibody that binds to OX40, activates the T cells to lead the charge against the cancer cells. Because the two agents are injected directly into the tumour, only T cells that have infiltrated it are activated. In effect, these T cells are “prescreened” by the body to recognise only cancer-specific proteins.
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Image credit: Stanford.