What are Natural Killer (NK) Cells?

The Importance of NK Cells in Immunotherapy

The immune system is a complex network of cells, tissues, and organs that work together to protect the body from infections, diseases, and foreign invaders. It plays a critical role in maintaining overall health and well-being by recognizing and responding to pathogens and abnormal cells. Without an effective immune system, the body would be vulnerable to a wide range of infections and diseases, some of which could be life-threatening.   

Natural killer (NK) cells are an important component of the immune system in identifying and eliminating abnormal cells.  NK cells help to modulate the immune response and maintain immune homeostasis within the body.

What are NK cells?

NK cells are a type of white blood cell that plays an important role in the innate immune system. NK cells are specialized immune effector cells, developing from the common progenitor as T and B cells.  NK cells have an innate ability to eliminate tumor cells, presenting great potential for use in cancer immunotherapies. They are called “natural” killers because they do not require prior activation to recognize and destroy infected or cancerous cells.

In addition to their direct killing abilities, NK cells play an immunomodulatory function by secreting cytokines and chemokines that enhance the body’s immune response. They are important in the early stages of immune response to viral infections and can also play a role in regulating the immune system’s response to cancer cells.

Sources of NK cells used in research and therapy include peripheral blood mononuclear cells (PBMCs), umbilical cord blood, and generation from induced pluripotent stem cells (iPSC).

Why are NK cells useful for cellular therapy research?

Below are a few of the key reasons why NK cells are important in cell therapy research:

• Cancer cell targeting – NK cells have the ability to recognize and destroy cancer cells, which makes them an ideal candidate for cancer immunotherapy. Cell therapy involving NK cells can be used to treat various types of cancer.
• Eliminating infected cells – NK cells can also target and eliminate infected cells, including cells infected with viruses. Cell therapy with NK cells has been used to treat viral infections like hepatitis B and C.
• Modulating immune responses – NK cells can modify the body’s immune response by interacting with other immune cells. For example, they can enhance the activity of T cells, another type of immune cell that plays an essential role in fighting infections and cancer.
• Lack of MHC restriction – Unlike other immune cells, NK cells do not require MHC (major histocompatibility complex) matching for recognition and activation. This makes them an attractive option for cell therapy, as they can be used in allogeneic (donor-derived) cell therapy without the need for matching.

How are scientists using NK cells in regenerative medicine?

NK cells are part of the body’s first line of defense against pathogens.  They are interesting to regenerative medicine because of their ability to quickly respond to abnormal cells and pathogens without requiring prior exposure.  NK cells recognize specific molecules on the target cells, which trigger the NK cell to release cytotoxic substances to destroy the target cell. 

Because NK cells have the ability to recognize and destroy cancer cells, they are often used in immunotherapy applications.  Cell therapy involving NK cells can be used to treat a wide variety of cancer.

NK cell applications in immunotherapy:

• Adoptive cell transfer – NK cells can be isolated from a patient’s own blood or from a donor, and then expanded in a lab. These expanded NK cells can then be transfused back into the patient as part of adopted cell therapy, which is often used in cancer immunotherapy, where the infused NK cells can recognize and kill the cancer cells.
• Antibody-dependent cell-mediated cytotoxicity (ADCC) – The process called ADCC refers to the use of monoclonal antibodies that target cancer cells and activate NK cells to destroy the tagged cancer cell.  This is used to enhance the efficacy of monoclonal antibody treatments in cancer immunotherapy.
• Combination therapy – NK cells can be used in combination with other therapies, such as checkpoint inhibitors, chemotherapy, and radiation therapy.  Combining NK cells with the traditional therapies can enhance the immune response and generate better outcomes.
• Gene editing – NK cells can be modified by gene editing to further enhance their function or their specific targets.  This includes NK cells engineered to express chimeric antigen receptors (CARs) that recognize specific molecules on cancer cells. 

In cell therapy applications, NK cells can be genetically modified to express chimeric antigen receptors (CARs) as an innovative type of cancer immunotherapy. CAR-NK cells express CARs that recognize a specific antigen uniquely expressed by target cells. CAR-NK cell therapy is an emerging alternate field to CAR-T cell therapies, accelerated by the ability to generate a homogeneously differentiated functional NK cell population from iPSCs that can be expanded to clinical scale as an “off-the-shelf” cell product.  CAR-NK cell therapy is a very promising approach to cancer immunotherapy.

Learn More

Want to learn more about NK cells and how they are being used in the fight against cancer? 

Check out the recent review on NK cell developments in cancer immunotherapy:

Veluchamy et al. The Rise of Allogeneic Natural Killer Cells As a Platform for Cancer Immunotherapy: Recent Innovations and Future Developments. Front. Immunol. 2017, Vol. 8, Article 631.

For more information about how Captivate Bio supports immune cell research and regenerative medicine, please visit our product catalog, services offerings, and knowledge center.