- Natural killer (NK) cells are white blood cells that have specialized roles as part of the body’s immune response and can kill tumor and infected cells through direct contact.
- While NK cells are potent first responders to infection and disease, they represent only a small proportion of all white blood cells and don’t endure for very long.
- Scientists are working hard to boost the cells’ effectiveness and persistence as NK cells have shown potential for use in cancer immunotherapy, though clinical application is still largely experimental.
Natural killer (NK) cells are white blood cells that serve as a part of the body’s first line of defense against infections and cancers. Along with T cells and B cells, NK cells have specialized roles as part of the immune system and have shown potential for being used in cancer immunotherapy. Their effectiveness is still being investigated; the use of NK cells in cancer treatment is not yet approved by the U.S. Food and Drug Administration.
How NK cells work
NK cells are potent first responders that can kill tumor and infected cells by direct contact, and they also can help regulate the immune system. Unlike T cells and B cells, NK cells can recognize and kill abnormal cells without ever having encountered the foreign cells or having had the foreign cells “presented” to them for recognition by MHC (major histocompatibility locus) molecules. However, NK cells make up a relatively small proportion of white blood cells, and they don’t endure for very long. Scientists are working hard to boost their effectiveness and endow them with “memory-like” powers for greater persistence.
T cells, on the other hand, make up a much larger part of the immune army. They aren’t first responders but go on the attack in a delayed fashion after having been primed to recognize specific identifying molecules, or antigens, on infected or cancerous cells. They also persist longer in the body. T cells are the immune soldiers that are unleashed against cancer by the checkpoint blocker drugs like pembrolizumab, nivolumab and ipilimumab.
“The unique capabilities of NK cells and T cells complement each other,” says Rizwan Romee, MD, a transplantation specialist at Dana-Farber who studies NK-based cellular therapy. “They make it possible for the immune system to recognize a broader array of diseased cells than it could with either NK or T cells alone.
“Infected or cancerous cells oftentimes have a certain group of molecules on their surface yelling for help, saying, basically, ‘We are infected, we are malignant, we have stress in our nucleus or genes.’ NK cells respond by becoming activated and killing the cells to prevent the infection or disease from spreading,” Romee explains.
NK cells also have an advantage in that they are relatively safe and less likely to cause graft versus host disease (GVHD) — where white blood cells present within the transplanted tissue attack the recipient’s body cells.
What’s the latest in NK cell research?
Along with other forms of immunotherapy, there is a great deal of research on how NK cells could be used to treat cancer.
In general, NK cells are harvested from healthy donors and activated by exposing them to various chemical signaling substances; they are then infused into the patient. There is a big push towards engineering NK cells to enhance their cancer targeting and prolonged persistence after infusing them into the patients.
Development of CAR NK cells where cells are armed with gene constructs aimed at binding to the various proteins expressed by cancer cells is one of the major areas of research in the field. CAR NK cells have several major advantages over CAR T cells including minimal risk of developing severe cytokine release syndrome (CRS) and neurotoxicity, two major and sometimes fatal complications routinely seen in patients after receiving CAR T cells.
Recent advances have allowed NK cells to be generated from induced Pluripotent Stem Cells (iPSCs) adult cells that have been reprogrammed back to an embryonic state where they can serve as a universal cell course for all types of cell therapies including cancer immunotherapies using NK cells.
Despite many advancements in the past few decades, nevertheless, clinical application of NK cells is still largely experimental and faces a number of challenges. They have so far found greater success in treating blood cancers than in attacking solid tumors, but research is proceeding on both fronts, with numerous clinical trials in progress.
Romee has been using NK cell-based therapy to treat patients who have relapsed after having had an haploidentical (half-matched donor) stem cell transplant for a blood cancer. A number of such patients received adoptively transferred memory-like NK cells followed by seven doses of interleukin-2 to stimulate the expansion of NK cells. In the first six patients of the phase 1 trial there was a 10 to 50-fold expansion of NK cells that was sustained over months. Romee commented that these NK cells “serve as a promising platform for the treatment of post-transplant relapse of myeloid disease.”
Research on using NK cell therapy in solid tumors is being conducted by Glenn Hanna, MD, at Dana-Farber, who is evaluating the safety and efficacy of a combination of NK donor cells and the immunotherapy drug ipilimumab in patients with advanced head and neck cancer.
There are currently hundreds of clinical trials of cancer treatment involving NK cells alone or in combinations, and despite the challenges that have thus far hindered them from winning FDA approval, many scientists believe they have a bright future.
About the Medical Reviewer
Dr. Hanna completed his fellowship training in hematology and medical oncology at Dana-Farber Cancer Institute in 2016. Prior to this, he earned his medical degree from Georgetown University School of Medicine in 2010, where he graduated summa cum laude, a member of Alpha Omega Alpha Honor Society and the Kober Medalist for academic excellence. He joined the faculty of the Center for Head and Neck Oncology in 2017. Dr. Hanna is the Director of the Center for Cancer Therapeutic Innovation (CCTI), the early drug development program at DFCI. His clinical and translational research efforts focus on precision medicine approaches to treat head and neck cancers. He has special interests in salivary gland cancers and rare head and neck malignancies, and in molecular and immunologic biomarker discovery.