A two-pronged immunotherapy approach can eliminate all traces of cancer in mice, according to a study by the Stanford University School of Medicine.
Researchers injected minute amounts of two immune-stimulating agents directly into solid tumours and found the approach worked for many different types of cancers, including those that arise spontaneously and also secondary, untreated metastases.
The scientists believe that the local application of these agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with body-wide 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 and senior author of the study, published in Science Translational Medicine.
“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.”
Immune cells, such as T cells, recognise and attack tumours, but as the tumour grows it becomes more difficult for the T cells to fight it.
But when the two agents are injected directly to the tumour site, they reactivate the cancer-specific T cells. One agent, 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.
There are many different approaches to immunotherapy—in which the aim is to harness the immune system to combat cancer—but, despite some being successful, each has downsides. These can range from high costs to intolerable side effects.
“Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumour itself,” said Levy.
“In the mice, we saw amazing, bodywide effects, including the elimination of tumours all over the animal.”
In the trial 87 out of 90 mice were cured of the cancer, and in the three mice where the cancer returned, the tumours regressed after a second treatment.
There are still many trials that the treatment needs to pass, but one agent is already approved for use in humans and the other has been tested for human use in several unrelated clinical trials.
A separate clinical trial was launched in January to test the effect of the treatment in patients with lymphoma and is expected to recruit about 15 patients with low-grade lymphoma.
If successful, Levy hopes the two agents could eventually be injected into solid tumours in humans prior to surgical removal of the cancer, preventing recurrence because of unidentified metastases or lingering cancer cells.
“I don’t think there’s a limit to the type of tumour we could potentially treat, as long as it has been infiltrated by the immune system,” Levy said.