Natural killer cells – or NK cells – are part of our immune system. They patrol our bodies for abnormal cells like cancer and destroy them. But cancer cells can make themselves invisible, making it much more difficult for NK cells to find them and do their job.
Through clinical research, MD Anderson is developing a new type of immunotherapy called CAR NK therapy. This type of treatment enhances the cancer-fighting power of NK cells.
“We’re trying to build on the natural ability of NK cells by giving them the skills to recognize and destroy cancer cells that have made themselves invisible,” says Katy Rezvani, M.D., Ph.D., co-leader of MD Anderson’s adoptive cell therapy platform.
Enhancing cancer-fighting ability of NK cells
Through the MD Anderson Cord Blood Bank, Rezvani and her team gather NK cells from donated umbilical cord blood and transform these cells into an effective cancer therapy.
“Our approach is to extract NK cells from the blood of an umbilical cord that’s been donated by parents after their baby's birth,” Rezvani says.
A molecule called a chimeric antigen receptor – or a CAR – is then added to the NK cells. With this addition, the new CAR NK cells can now recognize a target on the surface of the previously “invisible” cancer cell and attack. Current research has focused on a specific target molecule called CD19, which is found on certain cancer cells. Through the first CAR NK clinical trial, Rezvani and her team are treating patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma and acute lymphoblastic leukemia.
A ready-to-use blood cancer treatment option
Because CAR NK therapy uses cells from donated umbilical cord blood, it can potentially be made ahead of time and frozen for storage. This is different from some types of adoptive cellular therapy, like CAR T cell therapy, which can require a few weeks to prepare.
“From one cord blood donation, it is possible to generate hundreds of doses of CAR NK therapy to be used on multiple patients,” Rezvani says. “Our ultimate goal is to have an off-the-shelf product, so it’s ready for use as soon as the patient needs it.”
CAR NK therapy has two phases
Before you receive CAR NK therapy, you’ll receive chemotherapy for three consecutive days. The job of this chemotherapy isn’t to fight the cancer, but rather to prepare your body for the modified NK cells.
After a two-day break, you’ll then receive a single dose of CAR NK therapy. It’s delivered through one of your veins – just like a blood transfusion. “And then we wait for the cells to do their job,” Rezvani says.
CAR NK kills cancer quickly with few side effects
Through clinical trials, Rezvani and her team have learned CAR NK therapy attacks cancer quickly.
“We've seen the CAR NK cells work very rapidly,” says Rezvani of her team’s initial research, which was published in the Feb. 6 issue of the New England Journal of Medicine. Of the 11 patients treated on the study, eight responded to therapy and seven of those no longer showed evidence of disease at a median follow-up of 13.8 months. CAR NK cells also were seen in patients’ bodies one year after their treatment. This suggests the CAR NK cells are continuing to look for cancer cells and working long-term. Five of the patients who had no evidence of disease received post-remission therapy.
And, in the research to date, patients have had minimal side effects from the CAR NK cell therapy itself. “But we do see some side effects from the conditioning chemotherapy,” Rezvani says. The most common are nausea and a drop in blood counts, which can increase the risk of infection. These side effects typically appear within seven to 14 days of receiving the chemotherapy, but they can be easily managed.
“We can give medications to prevent nausea and infections, and occasionally we’ll give a blood transfusion to increase blood counts,” Rezvani says.
What’s next? Expanding CAR NK to treat more cancers
Because CAR NK therapy can be prepared in advance and has minimal side effects, Rezvani hopes to expand it to more types of cancer.
“In my lab, we’re working to develop CARs to recognize other targets on more cancer types, including breast cancer and glioblastoma,” Rezvani says. “We’re hoping to get the next generation of CAR NKs into the clinic quickly to benefit many more patients.”
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