Anti-aging health care -- one of clinical applications of NK cells
NK cells are the core participants in senescent cell immune surveillance. They increase with age, but their cytotoxicity and function continue to decline, which increases the incidence of infections, malignant tumors, inflammatory diseases and other diseases. Improving the senescence of NK cells plays an important role in treating age-related diseases and delaying the biological aging process [1]. In Japan, NK cell reinfusion has become normalized as an effective means of tumor treatment and anti-aging health care.
一、Research on the role of NK cells in enhancing immunity
In 2014, Guo Sumin et al. [2] found in "Research on the Effect of Autologous Cellular Immunotherapy on Fatigue and Cellular Immune Function in Sub-Healthy Populations" that autologous NK cell infusion can relieve fatigue symptoms and enhance their cellular immune function in sub-healthy populations. improve the quality of life. Criteria for determining NK cells: CD3 negative and CD16 or CD56 positive are NK cells. The method for preparation and reinfusion of NK cells is as follows: collect 50~80mL of peripheral blood to isolate mononuclear cells, activate and culture for 13~14 days, count the total number >1×109, detect no bacterial or fungal contamination, wash 3 times with normal saline, and reinfuse The endotoxin test is <0.5 EU/ml before reinfusion, and 20 mg of diphenhydramine is injected intramuscularly before reinfusion. For sub-healthy groups, autologous cell NK treatment is used for 4 cycles, with 1 cycle of treatment every 1 month.
二、Research on NK cells delaying aging
In 2022, Nickolas Chelyapov et al. [3] found that expanded and cultured autologous NK cells reduced senescence markers of PBMC in the blood after reinfusion. The study involved 5 volunteers who were divided into two groups: a group of three people received 1×109NK reinfusion, men aged 41, 50 and 70 years old respectively; a group of two persons received 2×109NK reinfusion, respectively. A 50-year-old woman and a 52-year-old man. After an average of 15 days of in vitro culture (range 14-19 days), aNK cells were harvested at the peak of the exponential expansion phase, and the median number of CD3(-)CD56(+) aNK cells (range 83.4-96.0%) was 91.0%. The research results showed that after infusion of NK cells, the p16 and β-gal levels of the five volunteers decreased to varying degrees, 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 for reinfusion therapy successfully killed senescent cells in mice or humans, and found that the senescent cell clearance ability of NK cells was significantly improved after combined with a dopamine-releasing peptide [ 4]. The study enrolled 26 volunteers who received NK cell infusions. The proportion and absolute number of peripheral blood NK cells and the purity of the NK cell product infused into each individual were inversely related to the age of the volunteer. The characteristics of volunteers and NK cell characteristics are shown in the table below:
一、Research on the role of NK cells in enhancing immunity
In 2014, Guo Sumin et al. [2] found in "Research on the Effect of Autologous Cellular Immunotherapy on Fatigue and Cellular Immune Function in Sub-Healthy Populations" that autologous NK cell infusion can relieve fatigue symptoms and enhance their cellular immune function in sub-healthy populations. improve the quality of life. Criteria for determining NK cells: CD3 negative and CD16 or CD56 positive are NK cells. The method for preparation and reinfusion of NK cells is as follows: collect 50~80mL of peripheral blood to isolate mononuclear cells, activate and culture for 13~14 days, count the total number >1×109, detect no bacterial or fungal contamination, wash 3 times with normal saline, and reinfuse The endotoxin test is <0.5 EU/ml before reinfusion, and 20 mg of diphenhydramine is injected intramuscularly before reinfusion. For sub-healthy groups, autologous cell NK treatment is used for 4 cycles, with 1 cycle of treatment every 1 month.
二、Research on NK cells delaying aging
In 2022, Nickolas Chelyapov et al. [3] found that expanded and cultured autologous NK cells reduced senescence markers of PBMC in the blood after reinfusion. The study involved 5 volunteers who were divided into two groups: a group of three people received 1×109NK reinfusion, men aged 41, 50 and 70 years old respectively; a group of two persons received 2×109NK reinfusion, respectively. A 50-year-old woman and a 52-year-old man. After an average of 15 days of in vitro culture (range 14-19 days), aNK cells were harvested at the peak of the exponential expansion phase, and the median number of CD3(-)CD56(+) aNK cells (range 83.4-96.0%) was 91.0%. The research results showed that after infusion of NK cells, the p16 and β-gal levels of the five volunteers decreased to varying degrees, 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 for reinfusion therapy successfully killed senescent cells in mice or humans, and found that the senescent cell clearance ability of NK cells was significantly improved after combined with a dopamine-releasing peptide [ 4]. The study enrolled 26 volunteers who received NK cell infusions. The proportion and absolute number of peripheral blood NK cells and the purity of the NK cell product infused into each individual were inversely related to the age of the volunteer. The characteristics of volunteers and NK cell characteristics are shown in the table below:
In 2022, the Blood Transfusion Department of Shanghai Changzheng Hospital, the Institute of Immunology of Shanghai Jiao Tong University and other units collaborated to confirm that the reinfusion of NK cells can significantly alleviate T cell aging and exhaustion and inhibit the key component SASP (senescence-associated secretory phenotype) [5]. The study recruited 37 middle-aged healthy participants, 32 of whom were intravenously injected with autologous expanded NK cells, and five of whom were intravenously injected with normal saline. Then, changes in senescent and exhausted T cells in peripheral blood, as well as levels of SASP-related factors in serum, were monitored by flow cytometry within 4 weeks after infusion. NK purity identification standard: CD56+/CD16+/CD3-, the purity is approximately 48-61%.
At present, Shenzhen Cell Valley’s NK cell preparation technology has reached international allogeneic transplantation standards. 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+). Within 2-3 weeks, 10 billion (1×1010) high-purity NK cells can be prepared and tested for their ability to kill tumor cells for clinical treatment or preclinical scientific research. For detailed data, please see the previous tweet "Research Progress | Shenzhen Cell Valley achieves major breakthrough in CAR-NK preparation technology". Those who are interested in NK cell research can contact the Shenzhen Cell Valley Marketing and Sales 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 researching cell and gene therapies, promoting emerging technologies and letting more people understand new developments in biomedicine. The content of this article is for information exchange only. This platform remains neutral with respect to the content, statements, and opinion judgments in the article, and does not represent the position and opinions of Shenzhen Cell Valley. The relevant information in this article should not be used for diagnosis or treatment, nor can it replace professional medical advice, and this public platform will not assume any responsibility. The final right of interpretation of the above statement belongs to this public platform. This statement will apply to articles shared on this platform at all times. Thank you for your cooperation!
Copyright statement: The copyright of the article belongs to Shenzhen Cell Valley. Individuals are welcome to forward it to their Moments. Any media or institution that reprints it on other platforms in any form without authorization will be considered an infringement. For reprint authorization, please reply "Reprint" on the "Shenzhen Cell Valley" WeChat official account 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 researching cell and gene therapies, promoting emerging technologies and letting more people understand new developments in biomedicine. The content of this article is for information exchange only. This platform remains neutral with respect to the content, statements, and opinion judgments in the article, and does not represent the position and opinions of Shenzhen Cell Valley. The relevant information in this article should not be used for diagnosis or treatment, nor can it replace professional medical advice, and this public platform will not assume any responsibility. The final right of interpretation of the above statement belongs to this public platform. This statement will apply to articles shared on this platform at all times. Thank you for your cooperation!
Copyright statement: The copyright of the article belongs to Shenzhen Cell Valley. Individuals are welcome to forward it to their Moments. Any media or institution that reprints it on other platforms in any form without authorization will be considered an infringement. For reprint authorization, please reply "Reprint" on the "Shenzhen Cell Valley" WeChat official account to obtain reprint instructions.
