Immunotherapy is a cut above chemotherapy and radiotherapy: at its best, it is significantly more effective and significantly less harmful to the patient. It has still required years, a great deal of funding, and many failures for those best approaches to arise. Nonetheless, the report here is a cheering example for the sizable fraction of us expected to suffer cancer at some point in the years ahead if the condition is not soon brought under medical control. This immunotherapy appears highly effective, and just importantly, adaptable to many types of cancer. This potential for broad application is the most important aspect of any potential new cancer therapy. There are hundreds of subtypes of cancer, and the research community cannot make acceptably rapid progress by dealing with them one at a time - too many years and too much funding has gone to that type of strategy in the past. The only viable way forward towards the control of cancer in our lifetime is the production of very general anti-cancer technologies, those that are effective and easily, quickly, and cheaply adapted to each type of cancer.
Injecting minute amounts of two immune-stimulating agents directly into solid tumors in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases. The approach works for many different types of cancers, including those that arise spontaneously. 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.
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 tumor 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. Cancers often exist in a strange kind of limbo with regard to the immune system. Immune cells like T cells recognize the abnormal proteins often present on cancer cells and infiltrate to attack the tumor. However, as the tumor grows, it often devises ways to suppress the activity of the T cells.
The new method works to reactivate the cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site. 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 tumor, only T cells that have infiltrated it are activated. In effect, these T cells are "prescreened" by the body to recognize only cancer-specific proteins. Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.
The approach worked startlingly well in laboratory mice with transplanted mouse lymphoma tumors in two sites on their bodies. Injecting one tumor site with the two agents caused the regression not just of the treated tumor, but also of the second, untreated tumor. In this way, 87 of 90 mice were cured of the cancer. Although the cancer recurred in three of the mice, the tumors again regressed after a second treatment. The researchers saw similar results in mice bearing breast, colon and melanoma tumors. "This is a very targeted approach. Only the tumor that shares the protein targets displayed by the treated site is affected. We're attacking specific targets without having to identify exactly what proteins the T cells are recognizing."