N K Cell immunotherapy – A new era in the treatment of cancer

Trillions of cells replicate in the human body every day, and under the influence of carcinogens such as smoking, ionizing radiation, and Helicobacter pylori, around 500,000 to 1 million cells can mutate during this replication process daily. The human body has developed a sophisticated immune defense system over thousands of years of evolution, with bone marrow serving as the headquarters where hematopoietic stem cells differentiate into immune fighters with different functions. The immune system is organized into three main armies: the core legion consisting of lymphocytes (T cells, B cells, and NK cells), the auxiliary legion responsible for antigen presentation (including macrophages and dendritic cells), and other immune cell groups such as neutrophils, eosinophils, and platelets.

Natural Killer (NK) cells are the first responders in the battle against cancer. They are the third group of lymphocytes alongside T and B cells, are large in size and contain cytoplasmic particles, and are directly derived from bone marrow. NK cells have three defining characteristics that make them uniquely powerful: they are part of the innate immune system and are the very first cells to attack tumor cells; they have a broad-spectrum antitumor effect that does not require tumor-specific recognition and is not restricted by the major histocompatibility complex (MHC); and they provide rapid situational feedback — the moment an abnormality is detected, they activate the entire immune defense and killing functions of the immune system. NK cells kill cancer cells through three main mechanisms: directly releasing perforin and granzyme or using death receptors to destroy tumor cells; activating cytokines and chemokines to stimulate T cells for amplified killing; and forming ADCC (antibody-dependent cell-mediated cytotoxicity) in coordination with B cells and macrophages, further enhancing cancer-killing capacity.

Despite their powerful cancer-fighting capabilities, NK cells account for only about 15% of total lymphocytes in peripheral blood and approximately 10% of white blood cells. Furthermore, after the age of 25, human immunity gradually declines and the number of NK cells decreases. In tumor patients and post-surgery patients, the number and activity of NK cells are further compromised, making it difficult for them to effectively exert their anticancer function. This is where NK cell therapy becomes critical.

Researchers are now focused on adoptive NK cell therapy — collecting NK cells from closely related donors and injecting them into patients. Unlike T cell therapy, NK cells do not cause graft-versus-host disease in recipient tissues, making them significantly safer. The current international NK cell strategies for tumor immunotherapy include in vitro activated autologous or allogeneic NK cell therapy, combining NK cells with monoclonal antibodies such as immune checkpoint inhibitors to induce antibody-specific cytotoxicity, and constructing CAR-NK cell immunotherapy — similar in concept to CAR-T therapy but using NK cells modified with chimeric antigen receptors to significantly improve targeting specificity.

The advantages of NK cell therapy are broad. It can effectively remove tumor cells that cannot be completely eliminated by surgery when combined with radiotherapy and chemotherapy, improve the efficacy of radiochemotherapy while reducing side effects, serve as a better option for advanced cancer patients who are not suitable for surgery or conventional therapies, prevent recurrence and metastasis after surgery through regular treatment, relieve cancer pain, improve sleep and quality of life, and even reduce cancer risk in sub-healthy individuals.

In Japan, scientists have developed a multiplication method to dramatically increase NK cell effectiveness. By extracting 50 ml of blood, isolating a small amount of NK cells, and expanding the culture to 1,000 times the original number — reaching 1 to 5 billion cells — these amplified NK cells are returned to the patient's body where they circulate 3,000 to 4,000 times through the blood system, killing cancer cells, aging cells, diseased cells, bacteria, and viruses throughout the body.

In the United States, NK cell therapy has been included in cancer immunotherapy clinical trials. A woman with acute myeloid leukemia (AML) who had failed repeated chemotherapy received an experimental infusion of NK cells donated by her son — within 4 days, her skin lesions disappeared and she entered remission. A clinical trial led by Washington University in St. Louis, which enrolled approximately 12 patients with AML and myelodysplastic syndrome (MDS), showed that half of the patients entered the remission period. MD Anderson and Dana-Farber Cancer Institute are also conducting clinical trials testing NK cell therapy efficacy in patients with hematological tumors that relapsed after stem cell transplantation.

A particularly compelling real-world case comes from an authoritative NK cell therapy clinic in Japan. Ms. Zheng, a 50-year-old patient diagnosed with advanced pancreatic cancer that had metastasized to the liver, lungs, and pleura — with cancerous peritonitis and multiple lung nodules — had a CA19-9 level that rose from 257,531 to 318,417 after one cycle of gemcitabine, and was given only three to six months to live. On expert recommendation, she began receiving highly activated NK cell infusions every two weeks. After the first treatment, her energy noticeably improved and pain symptoms were alleviated. After the first NK cell session, CA19-9 dropped dramatically to 7,355, and after the fourth treatment, it fell further to 141. By the end of 2016, CT imaging showed that metastatic lesions in the liver and lung bronchial lymph nodes had disappeared, and the primary pancreatic tumor had shrunk by more than half — a remarkable outcome that far exceeded expectations for a patient initially given only months to live