At the 2020 China Biotechnology Innovation Conference, Tian Zhigang, a professor at the Chinese University of Science and Technology and an academician of the China Academy of Engineering, said in the theme "Synthetic Immunology Technology and Tumor Immunotherapy" that in 2020, the charge of NK cell immunotherapy sounded: NK cells in allogeneic peripheral blood, iPSC-NK cells and umbilical cord blood entered large-scale amplification production; The curative effect of allogeneic CAR-NK cells is equivalent, which avoids the toxic and side effects of CAR-T cell therapy.
NK cells: a powerful pioneer in anti-tumor
In a healthy human body, immune cells constantly kill cancer cells formed by gene mutation of various cells, and maintain the balance between immunity and new cancer cells. With the decline of immunity, the number of immune cells gradually decreases, especially the fighting capacity of NK cells in the front line gradually decreases, so the balance of immune cells is broken in the battle to kill cancer cells, and the growth of cancer cells tends to be superior, leading to the risk of cancer. Therefore, reinfusion of NK immune cells through immunoamplification can increase the anti-cancer ability and play a role in cancer treatment.
A large number of clinical experiments have proved that NK cells can play an active role in the treatment of various cancers, so immunotherapy has been highly anticipated by researchers. However, the killing ability of NK cells is still limited, and the therapeutic effect on some solid tumors is still not ideal. In order to enhance the lethality of NK cells, the medical community began to study the use of NK cells to develop new immunotherapy for cancer. CAR-NK technology came into being.
CAR (chimeric antigen receptor) technology is a fusion technology of genetic engineering and immunotherapy, and it is one of the most promising research directions in the field of tumor treatment. The modified immune cells are like missiles with infrared guidance function, which can identify tumor cells and achieve precise killing.
2065438+In August 2008, researchers from the University of California, San Diego and the University of Minnesota published a new study in Cell Stem Cells. They used modified CAR-NK cells to effectively resist ovarian cancer in a mouse model. This research paves the way for the development of "ready-made" immunotherapy, which does not need to be customized for each patient.
In February 2020, researchers at the University of Texas at The University of Texas MD Anderson Cancer Center published the results of I/II clinical trials of allogeneic CAR-NK cell therapy for CD 19 in NEJM magazine: among 1 1 patients with relapsed/refractory CD 19 positive tumors (non-Hodgkin's lymphoma or chronic lymphoblastic leukemia),
Compared with CAR-T therapy, CAR-NK therapy can produce a large number of cells, and will not cause similar toxic reactions, with almost no side effects. In the most striking field of tumor immunotherapy, CAR-NK therapy has great application potential.
NK cells: the first line of defense against viruses
In recent years, NK cells have been gradually applied to antiviral therapy. It is found that it is involved in the immune response to many viruses (such as EB virus EBV, cytomegalovirus CMV, mouse pox virus ECTV, influenza A virus IAV, etc.). ).
20 16 An article published by Fang Min researcher's laboratory, Institute of Microbiology, China Academy of Sciences mentioned that NK cells can help to eliminate influenza A infection in 129 strain mice [2], and related research results were published in the International Journal of Immunology. It was found that NK cells significantly inhibited the replication of influenza virus in 129 mice infected with influenza virus and improved the survival rate of mice. Further mechanism research shows that NK cells can quickly rush to the lungs to play an anti-influenza virus infection role after 129 mice are infected with influenza virus.
NK cells are also involved in the therapeutic research of novel coronavirus.
On June 29th, 2020, sorrento Pharmaceutical Co., Ltd. and Celularity Cell Therapy Co., Ltd. jointly announced the start of clinical cooperation, aiming at extending the use of CYNK-00 1 (an allogeneic, placental-derived NK-damaged immune cell therapy) to the research on the treatment and prevention of coronavirus infection [3]. On February 2, 2020, the scientific research project of Henan Province "Clinical study of umbilical cord blood NK cells in the treatment of severe patients with coronavirus infection" was approved [4].
NK cells: enhancing immunity and preventing cancer
The research and practice of human life science have found that the decline of immune function and immunity is an obvious manifestation of human aging. When the physiological decline of immune function develops to a certain extent, the risk of autoimmune diseases and tumors is also increasing. Therefore, the aging of immune function is considered to be an important reason for the aging of the body.
Studies have shown that NK cells can directly improve and regulate human immunity and nervous system, secrete endorphins, relieve patients' pain and improve their quality of life. Autologous NK cell immunotherapy can obviously improve the fatigue and sleep quality of sub-health people and improve their quality of life.
Shi Jinfang, the First Affiliated Hospital of Suzhou University, and others discussed NK cells in the paper "Immune Aging and Early Warning Indicators of Immunology" published in Modern Immunology in 2005: "Studies show that the elderly over 100 can also effectively resist infection because their NK cell system has a good function and can migrate and effectively kill target cells, while the elderly with damaged NK cells are prone to influenza, tuberculosis and other diseases. Therefore, the decline in NK cell activity is a precursor to the disease, and maintaining NK cell activity helps to prolong life. "
It can be seen that how to increase the number of NK cells in the body has become the key for us to activate immunity and overcome cancer.
Significance of NK cell storage
Chen Lin, deputy director of the Regenerative Medicine Center of the 1 17 Hospital of the People's Liberation Army, once mentioned in the column of "Famous Medical Hall" that storing NK cells (a kind of immune cells) can supplement and strengthen the already weakened NK cells in the body, greatly improve the immunity, and reinfuse the immune cells into the body after expansion, and the clinical effect is very impressive [5].
In an interview with The Paper, researcher Shi of the Pathology Laboratory of Huaxi Hospital also mentioned that after being cultured in vitro, the number of human autoimmune cells has doubled by thousands, and the targeted killing function has been enhanced, and then reinjected into the human body, killing pathogens, cancer cells and mutant cells in blood and tissues, breaking immune tolerance, activating and enhancing the body's immune ability, and taking into account the dual effects of treatment and health care.
To sum up, immune cells have the functions of improving sub-health, anti-aging, anti-virus, anti-infection and anti-tumor. It is found that the immune status of different ages is very different, and younger immune cells can enhance the effect of cell therapy. Young immune cells even play an important role in the effectiveness of immunotherapy [6].
Because of this, the concept of storing healthy immune cells at a young age is becoming more and more popular all over the world. These stored immune cells are expected to become the key source of immune cell therapy in the future.
Source of information:
[ 1]? [endif] Paul Hudson of Sanofi paid $357 million to acquire a biotechnology partner and added a NK strategy, which is the latest measure to strengthen cancer research and development. D
[2]? [endif] Zhou Kai, Wang Jing, et al. Rapid and strong NK cell response protects 129 mice from high-dose influenza virus infection [J]. Journal of Immunology, 20 16, (2).
[3]? [endif]Sorrento and Celularity initiated the development of emergency allogeneic natural black (NK) cell therapy for coronavirus infection [N]. Global News Network, 2020-0 1-29.
[4]? [endif] Henan Provincial Department of Science and Technology. Henan launched the emergency scientific research project of prevention and control in novel coronavirus [N]. Henan Provincial People's Government, 2020-02-0 1.
[5]? Tony chen. Revealing the mysterious killer of cancer cells-NK cells [N]. Mingyitang,128:1112.
[6]? [endif]Donjete Simnica, Nuray Akyüz, et al. New generation sequencing of T cell receptors reveals tumor-related indicators and reconstruction in patients with hematological and solid tumors after chemotherapy [J]. Taylor Company. Francis Online, 20 19, (7).