Anti-aging health care -- one of clinical applications of NK cells
NK cells are the core participants in the immune surveillance of senescent cells, which increase with age, but their cytotoxicity and function continue to decline, which will increase the incidence of infections, malignant tumors, inflammatory diseases and other diseases. Improving the aging of NK cells plays an important role in the treatment of age-related diseases and the delay of biological aging [1]. In Japan, NK cell transfusion has been normalized as an effective means of tumor therapy and anti-aging care.
一、The study of NK cells to enhance immunity
In 2014, Guo Sumin et al. [2] found in the 《Study on the Effect of Autologous Cellular Immunotherapy on Fatigue and Cellular Immune Function in Sub-Healthy People》 that autologous NK cell infusion can alleviate fatigue symptoms of sub-healthy people, enhance their cellular immune function and improve their quality of life. Criteria for NK cells: CD3 negative and CD16 or CD56 positive NK cells. The methods of NK cell preparation and transfusion were as follows: 50~80mL of peripheral blood was collected and mononuclear cells were isolated. After activation and culture for 13~14 days, the total count was > 1×109. After detection of no bacterial or fungal contamination, normal saline was washed 3 times. Before transfusion, endotoxin test < 0.5EU/ml was detected, and 20mg diphenhydramine was injected intramuscular before transfusion. Sub-healthy population was treated with autologous cell NK for 4 cycles, 1 cycle every 1 month.
二、The study of NK cells to delay senescence
In 2022, Nickolas Chelyapov et al. [3] found that amplified cultured autologous NK cells reduced the aging marker of PBMC in the blood after transfusion. Five volunteers participated in the study, which was divided into two groups: a group of three received 1×109NK transfusion, respectively 41 years old, 50 years old and 70 years old men; One group of two people received 2×109NK transfusions, a 50-year-old female and a 52-year-old male. aNK cells were harvested at the peak of exponential expansion period after an average of 15 days in vitro (range 14-19 days), and the median number of CD3(-)CD56(+) aNK cells (range 83.4-96.0%) was 91.0%. The results of the study showed that p16 and β-gal levels of the five volunteers were reduced to varying degrees after the infusion of NK cells, indicating that NK cells can improve chronic inflammation and delay immune aging.
Recent studies by Chinese scholars have found that the use of NK cells to carry out transfusion therapy successfully killed senescent cells in mice or humans, and found that after combining with a dopamine-releasing peptide, the senescent cell clearing ability of NK cells has been significantly improved [4]. The study recruited 26 volunteers who received an infusion of NK cells. The proportion and absolute number of peripheral blood NK cells and the purity of NK cell products transfused into each individual were inversely correlated with the age of the volunteers. The characteristics and NK cell characteristics of the volunteers are shown in the following table:
一、The study of NK cells to enhance immunity
In 2014, Guo Sumin et al. [2] found in the 《Study on the Effect of Autologous Cellular Immunotherapy on Fatigue and Cellular Immune Function in Sub-Healthy People》 that autologous NK cell infusion can alleviate fatigue symptoms of sub-healthy people, enhance their cellular immune function and improve their quality of life. Criteria for NK cells: CD3 negative and CD16 or CD56 positive NK cells. The methods of NK cell preparation and transfusion were as follows: 50~80mL of peripheral blood was collected and mononuclear cells were isolated. After activation and culture for 13~14 days, the total count was > 1×109. After detection of no bacterial or fungal contamination, normal saline was washed 3 times. Before transfusion, endotoxin test < 0.5EU/ml was detected, and 20mg diphenhydramine was injected intramuscular before transfusion. Sub-healthy population was treated with autologous cell NK for 4 cycles, 1 cycle every 1 month.
二、The study of NK cells to delay senescence
In 2022, Nickolas Chelyapov et al. [3] found that amplified cultured autologous NK cells reduced the aging marker of PBMC in the blood after transfusion. Five volunteers participated in the study, which was divided into two groups: a group of three received 1×109NK transfusion, respectively 41 years old, 50 years old and 70 years old men; One group of two people received 2×109NK transfusions, a 50-year-old female and a 52-year-old male. aNK cells were harvested at the peak of exponential expansion period after an average of 15 days in vitro (range 14-19 days), and the median number of CD3(-)CD56(+) aNK cells (range 83.4-96.0%) was 91.0%. The results of the study showed that p16 and β-gal levels of the five volunteers were reduced to varying degrees after the infusion of NK cells, indicating that NK cells can improve chronic inflammation and delay immune aging.
Recent studies by Chinese scholars have found that the use of NK cells to carry out transfusion therapy successfully killed senescent cells in mice or humans, and found that after combining with a dopamine-releasing peptide, the senescent cell clearing ability of NK cells has been significantly improved [4]. The study recruited 26 volunteers who received an infusion of NK cells. The proportion and absolute number of peripheral blood NK cells and the purity of NK cell products transfused into each individual were inversely correlated with the age of the volunteers. The characteristics and NK cell characteristics of the volunteers are shown in the following table:
In 2022, the Blood transfusion Department of Shanghai Changzheng Hospital and the Institute of Immunology of Shanghai Jiao Tong University jointly confirmed that reinfusion of NK cells can significantly alleviate T cell senescence and failure, and inhibit the key component SASP(senescence related secretion phenotype) [5]. The study recruited 37 middle-aged healthy participants, 32 of whom were injected with autoamplified NK cells intravenously and 5 with saline intravenously. Then, changes in peripheral blood senescent and depleted T cells, as well as levels of SASP-related factors in serum, were monitored by flow cytometry within 4 weeks after infusion. NK purity identification criteria: CD56+/CD16+/CD3-, the purity is about 48-61%.
At present, the NK cell preparation technology of Shenzhen Cell Valley has reached the international standard of allotransplantation. NK purity is higher than 96% (CD56+CD3-),T cell content is less than 1% (CD3+), and B cell content is less than 0.1% (CD19+). 10 billion (1×1010) high-purity NK cells can be prepared within 2-3 weeks, and their killing ability on tumor cells can be tested for clinical treatment or preclinical scientific research. Detailed data can be seen in the previous tweet "Research progress | Shenzhen Cell Valley achieves major breakthrough in CAR-NK preparation process". Anyone interested in NK cell research can contact Shenzhen Cell Valley Sales and Marketing Department.
References:
1]Brauning A, Rae M, Zhu G, Fulton E, Admasu TD, Stolzing A, Sharma A. Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions. Cells. 2022 Mar 17;11(6):1017. doi: 10.3390/cells11061017. PMID: 35326467; PMCID: PMC8947539.
[2] Guo Sumin, Yang Yonghui, Wang Jianmei. Effect of autologous cell immunotherapy on fatigue and cellular immune function of sub-health population [J]. Hebei Medicine,2014,36(24):3726-3727.
[3] Chelyapov N, Nguyen TT, Gonzalez R. Autologous NK cells propagated and activated ex vivo decrease senescence markers in human PBMCs. Biochem Biophys Rep. 2022 Nov 11;32:101380. doi: 10.1016/j.bbrep.2022.101380. PMID: 36386442; PMCID: PMC9661662.
[4] Bai Z, Yang P, Yu F, Li Z, Yao Z, Martinez J, Li M, Xu H. Combining adoptive NK cell infusion with a dopamine-releasing peptide reduces senescent cells in aged mice. Cell Death Dis. 2022 Apr 5;13(4):305. doi: 10.1038/s41419-022-04562-w. PMID: 35383143; PMCID: PMC8983684.
[5] Tang X, Deng B, Zang A, He X, Zhou Y, Wang D, Li D, Dai X, Chen J, Zhang X, Liu Y, Xu Y, Chen J, Zheng W, Zhang L, Gao C, Yang H, Li B, Wang X. Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial. Front Immunol. 2022 Sep 29;13:940577. doi: 10.3389/fimmu.2022.940577. PMID: 36248873; PMCID: PMC9562930.
Disclaimer: Shenzhen Cell Valley is committed to the research of cell and gene therapy, in order to promote emerging technologies, so that more people understand the new development of biomedicine. The content of this article is only used for information exchange, and the platform remains neutral on the content, statements and opinions of the article, and does not represent the position and views of Shenzhen Cell Valley. The relevant information in this article shall not be used for diagnosis or treatment, and cannot replace professional medical advice, and this public platform will not assume any responsibility. The final interpretation of the content of the above statement belongs to the public platform, and this statement will apply to all the articles shared on the platform at all times, thank you for your cooperation!
Copyright note: The copyright of the article belongs to Shenzhen Cell Valley, welcome individuals to forward to the circle of friends, media or institutions without authorization, reproduced in any form to other platforms, will be regarded as infringement. Reprint authorization please reply "Reprint" in the "Shenzhen Cell Valley" wechat public number to obtain reprint instructions.
References:
1]Brauning A, Rae M, Zhu G, Fulton E, Admasu TD, Stolzing A, Sharma A. Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions. Cells. 2022 Mar 17;11(6):1017. doi: 10.3390/cells11061017. PMID: 35326467; PMCID: PMC8947539.
[2] Guo Sumin, Yang Yonghui, Wang Jianmei. Effect of autologous cell immunotherapy on fatigue and cellular immune function of sub-health population [J]. Hebei Medicine,2014,36(24):3726-3727.
[3] Chelyapov N, Nguyen TT, Gonzalez R. Autologous NK cells propagated and activated ex vivo decrease senescence markers in human PBMCs. Biochem Biophys Rep. 2022 Nov 11;32:101380. doi: 10.1016/j.bbrep.2022.101380. PMID: 36386442; PMCID: PMC9661662.
[4] Bai Z, Yang P, Yu F, Li Z, Yao Z, Martinez J, Li M, Xu H. Combining adoptive NK cell infusion with a dopamine-releasing peptide reduces senescent cells in aged mice. Cell Death Dis. 2022 Apr 5;13(4):305. doi: 10.1038/s41419-022-04562-w. PMID: 35383143; PMCID: PMC8983684.
[5] Tang X, Deng B, Zang A, He X, Zhou Y, Wang D, Li D, Dai X, Chen J, Zhang X, Liu Y, Xu Y, Chen J, Zheng W, Zhang L, Gao C, Yang H, Li B, Wang X. Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial. Front Immunol. 2022 Sep 29;13:940577. doi: 10.3389/fimmu.2022.940577. PMID: 36248873; PMCID: PMC9562930.
Disclaimer: Shenzhen Cell Valley is committed to the research of cell and gene therapy, in order to promote emerging technologies, so that more people understand the new development of biomedicine. The content of this article is only used for information exchange, and the platform remains neutral on the content, statements and opinions of the article, and does not represent the position and views of Shenzhen Cell Valley. The relevant information in this article shall not be used for diagnosis or treatment, and cannot replace professional medical advice, and this public platform will not assume any responsibility. The final interpretation of the content of the above statement belongs to the public platform, and this statement will apply to all the articles shared on the platform at all times, thank you for your cooperation!
Copyright note: The copyright of the article belongs to Shenzhen Cell Valley, welcome individuals to forward to the circle of friends, media or institutions without authorization, reproduced in any form to other platforms, will be regarded as infringement. Reprint authorization please reply "Reprint" in the "Shenzhen Cell Valley" wechat public number to obtain reprint instructions.
