Immunotherapies rev up a patient’s immune system to attack cancer. But immunotherapies are not equally effective in all patients. This has puzzled researchers. Thy have been searching for ways to make immunotherapies more effective.
Now, researchers at Washington University School of Medicine in St. Louis have combined two immunotherapy strategies into a single therapy and found, in studies in human cells and in mice, that the two together are more effective than either alone in treating certain blood cancers, such as leukemia.
The study appears online in the journal Blood.
The study finds it safer than CAR-T cell therapy, which has been approved by the FDA. In CAR-T cell therapy, T cells are engineered to target tumor cells.
Cell-based immunotherapies are most commonly used against blood cancers but can be harnessed against some solid tumors as well, such as prostate and lung tumors and melanoma.
In the new research, the scientists have harnessed the technology used to engineer CAR-T cells and, instead of modifying specialized immune cells called T cells, they have used similar technology to alter different immune cells called natural killer (NK) cells.
The resulting immunotherapy combines the benefits of both strategies and may reduce the side effects that are sometimes seen in CAR-T cell therapy. In some patients, for example, CAR-T cell therapy causes a cytokine storm, a life-threatening overreaction of the immune system.
“Immunotherapies show great promise for cancer therapy, but we need to make them more effective and more safe for more patients,” said co-senior author Todd A. Fehniger, MD, PhD, a professor of medicine.
“This combined approach builds on the treatment strategy that we developed for leukemia patients using natural killer cells. We can supercharge natural killer cells to enhance their ability to attack cancer cells. And at the same time, we can use the genetic engineering approaches of CAR cell therapy to direct the natural killer cells to a tumor target that would normally be overlooked by NK cells. It fundamentally changes the types of cancer that NK cells could be used to treat, both additional blood cancers and potentially solid tumors as well.”
“One aspect of this study I find most exciting is how nicely these hybrid NK cells expand in the mice to respond to their tumors,” said co-senior author Melissa Berrien-Elliott, PhD, an instructor in medicine. “We can provide a tiny dose and see an incredible amount of tumor control. To me, this highlights the potency of these cells, as well as their potential to expand once in the body, which is critical for translating these findings to the clinic.”
Fehniger also pointed out that an advantage of NK cells in general — and for biological reasons that the scientists are still working to understand — NK cells don’t trigger a dangerous immune response or the long-term side effects that T-cell therapy can cause in attacking the patient’s healthy tissues, a condition called graft-versus-host disease.
