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Medical physics

Medical physics

Cancer ‘vaccine’ eliminates tumours in mice

22 Feb 2018 Tami Freeman

Researchers at Stanford University have demonstrated that 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 (Sci. Transl. Med. 10 eaan4488).

PET images of vehicle-treated (control) and CpG-treated mice

Immunotherapy aims to harness the immune system to combat cancer. Immune cells such as T cells recognize 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 T cell activity. Lead author Idit Sagiv-Barfi and colleagues have developed a method that reactivates cancer-specific T cells.

The approach involves injecting microgram amounts of two agents directly into a tumour site. One, a short stretch of DNA called CpG, works with other nearby immune cells to amplify expression of an activating receptor called OX40 on the surface of the T cells. The other, an antibody called anti-OX40, activates the T cells to attack the cancer cells. The researchers determined that some of these tumour-specific, activated T cells then leave the original site to find and destroy identical tumours elsewhere in the body.

The researchers believe that local application of very small amounts of these two agents could provide a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with bodywide immune stimulation.

The Stanford team tested this in situ vaccination approach on laboratory mice with tumours transplanted in two sites on their bodies. Injecting one tumour with CpG and anti-OX40 not only shrank this tumour, but caused regression of the second, untreated tumour. The treatment cured 87 of 90 mice of the cancer. Although secondary tumours recurred in three of the mice, these again regressed after a second treatment.

The researchers also examined mice genetically engineered to spontaneously develop highly invasive breast cancers in all 10 of their mammary pads. Treating the first tumour that arose often prevented the occurrence of future tumours and significantly increased the animals’ life span.

“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,” said senior author Ronald Levy. “This approach bypasses the need to identify tumour-specific immune targets and doesn’t require wholesale activation of the immune system or customization 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 unrelated trials. A clinical trial of this treatment was launched in January to test its effect in patients with lymphoma. The trial is expected to recruit about 15 patients and, if successful, the treatment may prove useful for many tumour types.

Levy envisions a future in which clinicians inject the two agents into solid tumours in humans prior to surgical removal of the cancer as a way to prevent recurrence due to unidentified metastases or lingering cancer cells, or even to head off the development of future tumours that arise due to genetic mutations. “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,” he said.

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