Anti-cancer effects of NK from different sources such as peripheral blood and umbilical cord blood
Introduction
In the minds of most people today, cancer is still an incurable disease. Both the illness experience and the traditional treatment process are very painful, the probability of recurrence is extremely high, and the number of cancer patients is increasing rapidly year by year, which also makes people talk about "cancer" in a different way. However, with the continuous development of biomedical technology, scientists have invented a cell therapy method called "CAR-T", which has greatly enhanced the treatment effect against cancer. The principle is to equip our body's immune guardian "T cells" with a high-tech weapon "CAR" (chimeric antigen receptor) to enhance its ability to recognize and kill tumor cells.
CAR-T cell therapy has gradually matured with the discovery of effective targets and the continuous improvement of CAR, and has made great achievements in conquering a wide variety of cancers, especially lymphomas, leukemias and other malignant hematological tumors. However, this has not satisfied scientists' expectations. With the hope and exploration of completely conquering cancer, a new type of anti-cancer warrior was born - CAR-NK. The principle behind it is to use genetic engineering technology to equip NK cells with the high-tech weapon "CAR".
The process of constructing CAR-NK cell immunotherapy
01
Since the addition of "CAR-NK", we have been in a strong position in the "war" against tumors! Although both "warriors" are experts in anti-cancer, "CAR-NK" has some unique advantages over "CAR-T" in the treatment of solid tumors. Let's take a look at the advantages of CAR-NK! (Shenzhen Cell Valley has domestic high-level CAR-NK preparation capabilities. For details, please review "Research Progress | Shenzhen Cell Valley achieves major breakthrough in CAR-NK preparation technology")
02
Now that the advantages of "CAR-NK" have been mentioned, we have to talk about the birthplace of this "hero". Currently, there are four main sources of NK cells in CAR-NK therapy: human peripheral blood (PB), umbilical cord blood (CB), stem cell-derived NK cells, and NK-92 cell lines.
Although NK cells may be born differently, their deep hatred of cancer cells has never changed. The ultimate goal is to "destroy" all cancer cells. Then let us learn about the birth story of this "hero".
03
Among these four sources of NK cells, peripheral blood NK cells and umbilical cord blood NK cells appear more frequently. The former is the most clinically used. The two "brothers" have their own characteristics in fighting solid tumors. There are also differences in efficacy in CAR-NK therapy (for details, please review the previous tweet "Comparison of CAR-NK cells derived from adult peripheral blood and umbilical cord blood"), which mainly depends on a variety of factors including the quality of the cell source. , preparation technology, etc. Regardless of whether it is CAR-NK prepared from NK cells derived from PB or CB, the viability and purity of Shenzhen Cell Valley preparations are above 90%, the positive rate of CAR transduction is as high as 60~80%, and the amplification factor can reach tens of thousands of times.
These two "brothers" are both "born" in the bone marrow and are our body's first line of defense against cancer. Not only that, "their" reaction speed is also one of the best. "They" are particularly "sensitive" to various pathogens and harmful cells that harm the body. They are always vigilant. As soon as these "bad guys" appear in our bodies, they will Can react immediately to eliminate them. Of course, all the credit for this is due to "their" ability to release the "killer weapon" that scares these "bad guys" - cytotoxic particles. These particles can cause target cells to undergo apoptosis or programmed cell death.
From the sharpening of Bao Jianfeng, the peripheral blood NK cells as the "boss" are not only "mature", but also spread throughout the circulatory system of the body. On the contrary, the "second child" umbilical cord blood NK cells only come from immature immune cells found in the umbilical cord of the fetus at birth, so they are slightly less experienced in fighting cancer. But precisely because the "second child" is so "young", there is more room for differentiation and development in the future. He mainly plays an important role in the fields of regenerative medicine such as cerebral palsy, autism, and stroke, breaking out another new world of his own.
As the "boss", peripheral blood NK cells have a more diverse population and greater functional variability due to their "maturity" and "experience", which can also better help "them" deal with various threats. , even more comfortable in the complex "big environment" of fighting cancer. As the "second child", umbilical cord blood NK cells have a low degree of differentiation, relatively limited diversity, lack of experience in dealing with cancer cells, and a slightly weaker ability to attack cancer cells.
In general, although the two "brothers" have different origins, "they" are both our "effective warriors" on the road to fighting cancer, and they have brought the dawn of dawn to mankind in this difficult to overcome cancer level. On this long-lasting and arduous "battlefield" against solid tumors, the "eldest" relies on his "maturity and stability" and "excellent skills" to have a better anti-killing effect and has made a lot of achievements; although the "second" is better than the "second" The "Big Brother" has weak direct killing ability, but it has important applications in hematopoietic stem cell transplantation and regenerative medicine. It can be said that "they" are all "shining" in their respective fields and benefiting mankind!
References
[1] Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, et al. CAR-transduced natural killer cells in CD19-positive lymphoid neoplasms. N England Medical Journal. 2020;382(6):545–53
[2] Gong, Y., et al., Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy. Journal of Hematology & Oncology, 2021. 14(1): p. 73
[3]Xie G. Z., Dong H., Liang Y., et al. CAR-NK cells: A promising cellular immunotherapy for cancer. EBioMedicine, 2020, 59: 102975
Disclaimer: Shenzhen Cell Valley is committed to the research of cell and gene therapy, in order to promote emerging technologies and let more people understand the 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, and cannot replace professional medical advice. Our website will not assume any responsibility.The final interpretation of the above statement belongs to our company’s website. This statement will apply to articles shared on our website 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 friends, media or Any unauthorized reproduction by the organization to other platforms will be regarded as infringement.If you need to reprint, please contact email: contact@duanglink.com Since the addition of "CAR-NK", we have been in a strong position in the "war" against tumors! Although both "warriors" are experts in anti-cancer, "CAR-NK" has some unique advantages over "CAR-T" in the treatment of solid tumors. Let's take a look at the advantages of CAR-NK! (Shenzhen Cell Valley has domestic high-level CAR-NK preparation capabilities. For details, please review "Research Progress | Shenzhen Cell Valley achieves major breakthrough in CAR-NK preparation technology")
| CAR-T细胞 | CAR-NK细胞 | |
Efficiency |
Antigen-specific priming is required to provide therapeutic anticancer effects, and the onset of action is relatively slow. |
It has stronger infiltration ability and killing effect in the treatment of solid tumors, can better identify and attack solid tumor cells, can provide therapeutic anti-cancer effects without any antigen-specific priming, and has a faster onset of action. |
Safety |
Allogeneic T cell interactions with human leukocyte antigen (HLA) complexes may lead to fatal cytokine release syndrome or graft-versus-host disease | CAR-NK cell treatment does not require myeloablative pretreatment, and NK cells have much fewer choices for (HLA) complexes, reducing toxicity and adverse reactions during treatment. |
The impact of tumor microenvironment |
The immunosuppressive microenvironment inside solid tumors, high extracellular potassium ion levels, hypoxia, low pH, high reactive oxygen species and adenosine levels are not conducive to the function of CAR-T cells. | CAR-NK cells are more adaptable to the tumor microenvironment and can better adapt to the internal environment of different tumors and improve the therapeutic effect. |
Immunomodulatory effect |
Regulatory T cells, myeloid-derived suppressor cells, M2 tumor-associated macrophages and other patient autologous cells often participate in the production of immunosuppression within tumors, and also provide tumor cells with cytokines and chemokines that promote growth and metastasis. | CAR-NK cells not only have a direct killing effect, but also regulate the immune response in the body and promote the recovery and balance of the immune system. |
Production and quality control |
Personalized customization is time-consuming and labor-intensive, difficult to expand, and has a high failure rate. The entire CAR-T preparation process is very complex, and the corresponding optimization of the production process is relatively slow. Considerable variable factors may cause variations in CAR-T cell manufacturing. | Do not cause graft-versus-host disease (GVHD), so they can be given from donor to recipient without the need for matching. This means that multiple doses of CAR-NK cells can be prepared from one donor to treat multiple patients, thereby greatly shortening the treatment time, and the production process is relatively simple and easy to control quality. |
Now that the advantages of "CAR-NK" have been mentioned, we have to talk about the birthplace of this "hero". Currently, there are four main sources of NK cells in CAR-NK therapy: human peripheral blood (PB), umbilical cord blood (CB), stem cell-derived NK cells, and NK-92 cell lines.
Although NK cells may be born differently, their deep hatred of cancer cells has never changed. The ultimate goal is to "destroy" all cancer cells. Then let us learn about the birth story of this "hero".
| Source of NK cells | Advantages | Disadvantages |
Human peripheral blood (PB) cells |
NK cells can be relatively easily isolated and expanded from patients themselves (autologous PB-NK) or healthy donors (allogeneic PB-NK), so most preclinical CAR-NK studies use PB-NK. Limited by disease and treatment, the function of patients' autologous NK cells may be impaired. Clinically, allogeneic NK cells are preferred, but the T cells must be carefully removed to reduce the occurrence of GVHD. PB-NK cells are mature, do not need to induce differentiation, and have strong killing effect. | 1. Due to cryopreservation of allogeneic PB-NK, cell viability and cytotoxicity are significantly reduced; 2. The gene transduction efficiency is relatively low, and the in vitro amplification time is prolonged, which affects the cell killing function; 3. It is usually necessary to infuse 105-108 cells/body weight (kg), but the ratio of PB-NK cells is low and large-scale culture in vitro is difficult. With its strong R&D capabilities, Shenzhen Cell Valley has successfully broken through the above bottlenecks and is able to provide high quantity, high purity, high gene transduction rate, and strong killing PB-NK cells. |
Cord blood (CB) NK cells |
"off-the-shelf", ready to use when needed, freeze-resistant. CB-NK has a high proliferation efficiency and can instantly select HLA-mismatched products by establishing a universal NK cell bank. Has stronger bone marrow homing ability. Umbilical cord blood cells have a strong ability to proliferate. Only 10% of one cord blood unit can produce a pure cell pool of almost more than 109 NK cells within two weeks, which is usually suitable for one treatment cycle. | CB-NK cells are not fully differentiated, have relatively low expression of natural killer receptors, and have limited cell killing ability. In addition, the higher proportion of hemoglobin and red blood cells in cord blood will affect the isolation and culture of PBM, which needs to be paid attention to during the experiment. |
Stem cell-derived NK cells |
NK cells are usually induced from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs), and the expansion cycle is 3-5 weeks, which can avoid the heterogeneity of NK cells between the recipient and the donor. | NK cells induced by iPSCs have the potential for malignant transformation and are at risk of tumorigenesis in the body; they are also potentially immunogenic and may trigger unexpected immune responses. |
NK-92 cell line |
"off-the-shelf", ready for use when needed, convenient for cell line expansion and activity maintenance. NK-92 lacks the CD16 receptor-mediated ADCC effect, but it can be obtained through modification. NK-92 cells are easy to perform genetic manipulation without the need for viral vectors, and foreign genes can be effectively introduced using electroporation. | Since NK-92 is a tumor-derived aneuploid immortalized cell, it needs to be irradiated before use, which inhibits its proliferation process in the body, has a limited lifespan, and reduces the RK and efficacy in the body. |
03
Among these four sources of NK cells, peripheral blood NK cells and umbilical cord blood NK cells appear more frequently. The former is the most clinically used. The two "brothers" have their own characteristics in fighting solid tumors. There are also differences in efficacy in CAR-NK therapy (for details, please review the previous tweet "Comparison of CAR-NK cells derived from adult peripheral blood and umbilical cord blood"), which mainly depends on a variety of factors including the quality of the cell source. , preparation technology, etc. Regardless of whether it is CAR-NK prepared from NK cells derived from PB or CB, the viability and purity of Shenzhen Cell Valley preparations are above 90%, the positive rate of CAR transduction is as high as 60~80%, and the amplification factor can reach tens of thousands of times.
These two "brothers" are both "born" in the bone marrow and are our body's first line of defense against cancer. Not only that, "their" reaction speed is also one of the best. "They" are particularly "sensitive" to various pathogens and harmful cells that harm the body. They are always vigilant. As soon as these "bad guys" appear in our bodies, they will Can react immediately to eliminate them. Of course, all the credit for this is due to "their" ability to release the "killer weapon" that scares these "bad guys" - cytotoxic particles. These particles can cause target cells to undergo apoptosis or programmed cell death.
From the sharpening of Bao Jianfeng, the peripheral blood NK cells as the "boss" are not only "mature", but also spread throughout the circulatory system of the body. On the contrary, the "second child" umbilical cord blood NK cells only come from immature immune cells found in the umbilical cord of the fetus at birth, so they are slightly less experienced in fighting cancer. But precisely because the "second child" is so "young", there is more room for differentiation and development in the future. He mainly plays an important role in the fields of regenerative medicine such as cerebral palsy, autism, and stroke, breaking out another new world of his own.
As the "boss", peripheral blood NK cells have a more diverse population and greater functional variability due to their "maturity" and "experience", which can also better help "them" deal with various threats. , even more comfortable in the complex "big environment" of fighting cancer. As the "second child", umbilical cord blood NK cells have a low degree of differentiation, relatively limited diversity, lack of experience in dealing with cancer cells, and a slightly weaker ability to attack cancer cells.
In general, although the two "brothers" have different origins, "they" are both our "effective warriors" on the road to fighting cancer, and they have brought the dawn of dawn to mankind in this difficult to overcome cancer level. On this long-lasting and arduous "battlefield" against solid tumors, the "eldest" relies on his "maturity and stability" and "excellent skills" to have a better anti-killing effect and has made a lot of achievements; although the "second" is better than the "second" The "Big Brother" has weak direct killing ability, but it has important applications in hematopoietic stem cell transplantation and regenerative medicine. It can be said that "they" are all "shining" in their respective fields and benefiting mankind!
Four sources of CAR-NK (from Clin Transl Immunology. 2021 Apr 28;10(4):e1274.)
References
[1] Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, et al. CAR-transduced natural killer cells in CD19-positive lymphoid neoplasms. N England Medical Journal. 2020;382(6):545–53
[2] Gong, Y., et al., Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy. Journal of Hematology & Oncology, 2021. 14(1): p. 73
[3]Xie G. Z., Dong H., Liang Y., et al. CAR-NK cells: A promising cellular immunotherapy for cancer. EBioMedicine, 2020, 59: 102975
