Injecting small amounts of two immunostimulating agents directly into solid tumors in mice can eliminate all traces of cancer, including distant and untreated metastases, according to a study by researchers at Stanford University School of Medicine (USA) and published in the journal Science Translational Medicine.
This technique works in many different types of cancers, including those that arise spontaneously, according to the scientists, who believe that the local application of very small amounts of these agents could serve as a rapid and relatively inexpensive therapy against cancer. Furthermore, it is unlikely to cause the adverse side effects often seen with immune stimulation throughout the body as occurs with traditional treatments.
“When we used these two agents together, we saw the elimination of tumors throughout the body. This approach avoids the need to identify tumor-specific immune targets and does not require wholesale activation of the immune system or customization of immune cells from a patient “, clarifies Ronald Levy, leader of the work.
One of the agents has already been approved for use in humans ; the other has been tested for human use in several unrelated clinical trials. And a clinical trial has already been launched to evaluate the effect of treatment in patients with lymphoma.
Levy is a pioneer in the field of cancer immunotherapy, in which researchers try to harness the immune system to fight 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.
Many of the current approaches, while successful, also have drawbacks, from unwieldy side effects to costly preparation or treatment times.
“All of these advances in immunotherapy are changing medical practice. Our approach uses a single application of very small amounts of two agents to stimulate immune cells only within the tumor. In mice, we saw surprising effects throughout the body, including elimination of tumors throughout the animal, “explains Levy.
Cancers often exist in a strange kind of limbo with respect to the immune system. Immune cells like T cells recognize abnormal proteins that are often present in cancer cells and infiltrate to attack the tumor. However, as the tumor grows, it often devises ways to suppress T-cell activity.
Levy’s method works to reactivate cancer-specific T cells by injecting micrograms of two agents, directly at the tumor site: CpG oligonucleotide, which works with other nearby immune cells to amplify the expression of an activating receptor called OX40 on the surface of T cells and an antibody that binds to OX40, which activates T cells to direct the charge against cancer cells.
Destroying cancer
The technique worked surprisingly well in laboratory mice with transplanted mouse lymphoma tumors in two places on their bodies. Injecting a single area of the tumor with the two agents caused regression not only of the treated tumor, but also of the second untreated tumor. In this way, 87 out of 90 mice were cured of cancer.
Although the cancer reappeared in 3 of the mice, the tumors regressed again after a second treatment. The researchers observed similar results in mice with tumors of the breast, colon, and melanoma.
Regarding the current clinical trial with about 15 human patients with low-grade lymphoma, if successful, Levy believes that the treatment could be useful for many types of tumors. Imagine a future in which doctors inject the two agents into solid human tumors prior to surgical removal of the cancer as a way to prevent recurrence or even to prevent the development of future tumors due to genetic mutations such as BRCA1 and 2.
“I don’t think there is a limit to the type of tumor that we could potentially treat,” Levy said.
Reference: I. Sagiv-Barfi el al., “Eradication of spontaneous malignancy by local immunotherapy,” Science Translational Medicine (2018) Vol. 10, Issue 426, eaan4488 DOI: 10.1126 / scitranslmed.aan4488
