Cell therapy research status
一、Overview of cell therapy
Cell therapy refers to the transplantation or input of normal or bioengineered human cells into the patient, and the newly imported cells can replace the damaged cells, or have a stronger immune killing ability, so as to achieve the purpose of treating diseases. According to cell type, it can be divided into stem cell therapy and immune cell therapy. The stem cells used in clinical treatment mainly include bone marrow stem cells, hematopoietic stem cells, neural stem cells, skin stem cells, islet stem cells, fat stem cells and so on. Stem cell therapy uses the differentiation and repair principle of human stem cells to transplant healthy stem cells into the patient's body to repair diseased cells or rebuild normal functioning cells and tissues. Immune cell therapy is to collect immune cells from the human body, culture them in vitro, increase their number by thousands of times, or modify immune cells to make them become cells with enhanced targeted killing function, and then inject them back into the human body to kill pathogens, cancer cells, and mutant cells in the blood and tissues, break immune tolerance, and activate and enhance the body's immune capacity.
二、Immune cell therapy
(1)chimeric antigen receptor T-cell (CAR-T) : The fastest growing and most widely used branch of cellular immunotherapy. This latest technology is rapidly changing the landscape of hematological malignancies and accounts for more than half of all cell therapies currently in development or on the market [1, 2]. CAR-T refers to the transfer of genetic material with specific antigen recognition domain and T cell activation signal into T cells through gene modification technology, so that T cells can directly bind to the specific antigen on the tumor surface to achieve precise targeted therapy, which is a very promising tumor treatment [3]. The current mainstream technology is the second generation of CAR, and on the basis of the first generation, an immunoreceptor tyrosine-based activation motif from the co-stimulatory molecule CD28 or CD137 (4-1BB) is added into the cell. Therefore, the activation ability and killing activity of the second generation CAR is much stronger than that of the first generation, and it also shows a good therapeutic effect in clinical treatment. The third and fourth generation cars are all under development and are currently in the pre-clinical research stage, and their efficacy is worth expecting [4]. Although CAR-T cells have shown good results in the treatment of B-cell leukemia and lymphoma, there are currently six CAR-T drugs approved by the US Food and Drug Administration (FDA) and three CAR-T products approved by the State Drug Administration. Although CAR T cell drugs have shown great advantages in hematoma, they also have their own limitations, mainly manifested in poor treatment effect of solid tumor, relapse of drug resistance after treatment, and side effects in some patients. Researchers are also working to find novel target antigens, optimize CAR structure, and combine CAR-T with other therapies to further improve its efficacy.
(2)CAR-NK: Natural Killer (NK) cells are an important part of innate immunity in the body. Compared with T cells, NK cells have many advantages in the application of CAR. Allogeneic NK cells do not cause graft-versus-host disease (GVHD). NK cell therapy does not secrete inflammatory cytokines (IL-1, IL-6), and almost does not cause the occurrence of cytokine release syndrome. NK cells have more tumor killing pathways, such as performing cell degranulation, activating apoptosis pathways, and mediating antibody-dependent cell-mediated cytotoxic functions (ADCC). Allogeneic NK cells come from a wide range of sources, including peripheral blood, umbilical cord blood, NK cell line (NK92) and induced pluripotent stem cell (iPSC-NK). NK cells have a short survival cycle in vivo, which is different from CAR T cells, which have a long retention period and are prone to side effects and attack the patient's own cells. The treatment of solid tumors has obvious advantages, because solid tumors show varying degrees of tolerance to unmodified NK cells, but are sensitive to antigen-dependent NK cells. The above advantages make CAR-NK have great potential and broad prospect in tumor immunotherapy [5].
(3)CAR-NKT: Natural Killer-T (NKT) cells are congenital T lymphocytes. Unlike NK cells, the target recognition of NKT cells is restricted by CD1d, similar to the recognition target of T cells is restricted by HLA. Although most tumors are CD1D-negative and cannot be directly targeted by NKT cells, NKT cells migrate to tumor sites in response to tumor-derived chemokines, and in some tumor types, the presence of NKT cells in primary tumors is associated with a favorable prognosis. Within tumors, tumor-associated macrophages stimulate angiogenesis, promote tumor growth and invasion, and mediate immunosuppression, and NKT cells are capable of killing such cells. In addition, NKT cell activation can indirectly promote the anti-tumor response mediated by NK cells and T cells. Although the amount of NKT cells in the blood is small, based on the above advantages of NKT cells, it has great potential in the development of cancer cell therapy [6]. In the published interim phase 1 clinical data of CAR-NKT for neuroblastoma, 1 out of 3 patients who received the therapy achieved objective remission and bone metastases subsided [7].
(4)CAR-M: In the tumor microenvironment, macrophage is a native immune cell with the highest invasion rate and interacts with almost all cellular components in the tumor microenvironment including tumor cells, immune cells such as T cells, NK cells, DC and other resident non-immune cells [8]. The above characteristics have also generated great interest in the development of CAR-M. Macrophages are usually the first immune cells to be absorbed by solid tumors, and CAR can help macrophages accurately recognize tumor cells, avoid being absorbed, and in turn engulf tumor cells. CAR-M can also present cancer cell antigen fragments to T cells, activate T cells, and promote anti-cancer immunity [9]. At present, clinical trials of CAR-M are still in the research and development stage, and no results have been reported.
(5) T cell receptor T (TCR-T) : Tcr-t cell therapy introduces the tumor antigen-specific TCR gene screened in vitro into T cells in vitro by means of genetic engineering. By infusing TCR-T cells carrying exogenous TCR gene into patients, the anti-tumor immunity of the body can be reestablished, thus achieving the purpose of tumor treatment. Compared with CAR T cell therapy, TCR-T cell therapy has certain uniqueness. First, TCR can recruit the naturally occurring CD3 subunit in T cells to generate an immune response. CAR intracellular activation generally depends on the intracellular domain of CD3ζ, with 3 ITams, while the intracellular receptor domain of the TCR/CD3 complex has 10 ITams [10]. Secondly, the formation of immune synapses between TCR-T cells and target cells can recruit a variety of molecules to produce synergies. Third, TCR-T cells are more sensitive to antigen than CAR-T cells. Because TCR-T cell therapy has the unique advantage of targeting tumor intracellular antigens, it has become an important potential method for the treatment of solid tumors.
三、Selection of virus vector
The key of cell therapy is the design of gene transduction vector. The virus has the function of transmitting its genome into the recipient cell for infection, so it can be used as a delivery vector to bring the target gene into the target cell. Common viral vectors include retrovirus vector, lentiviral vector, adenovirus vector, adeno-associated virus and non-viral vector, among which retrovirus vector and lentiviral vector are the most widely used in cell therapy. Lentiviral vector is a single stranded RNA virus, which can randomly insert foreign fragments into the genome of host cells. Lentiviral vector has the advantages of short instantaneous transfection and packaging cycle, and can infect both dividing and non-dividing cells. Retroviral vector is a spherical virus with envelope, which also carries its genetic material in the form of RNA and randomly integrates into the genome of host cells. It can infect dividing cells, carry large gene fragments, and infect T cells, NK cells and other cells with high efficiency. In terms of industrial production, lentiviral vector adopts instantaneous packaging system, large amount of plasmids, complex purification process, and low titer of viral vector (requiring complex purification and concentration), while industrial production of retroviral vector can prepare stable virus-producing cell lines, less amount of plasmids, low impurity content, and high titer of viral vector. Due to the above advantages, the number of R&D pipelines using retroviral vectors in the field of cellular gene therapy has significantly exceeded the number of R&D pipelines using lentiviral vectors globally. At present, lentivirus vectors are mainly used in various R&D pipelines in China, and it is expected that retrovirus vectors will also be widely used in China in the future [11, 12].
At present, there are 9 CAR-T products on the market worldwide, of which 6 are using lentiviral vector technology and 3 are using retrovirus vector technology
四、Summary
With the market and application of CAR-T cell therapy, immune cell therapy has gradually played an irreplaceable role in tumor therapy relying on its unique advantages. CAR-NK cell therapy can overcome some limitations of CAR-T, such as graft-versus-host disease and cytokine release syndrome. CAR-NK therapy is a rising star of cell products due to its advantages such as reduced toxicity and easy preparation of general-purpose products. CAR-M cell therapy launches a multi-pronged attack on tumors by combining the innate immune system and the adaptive immune system [13]. Meanwhile, TCR-T cell therapy has shown very encouraging results in solid tumors [14]. In summary, immune cell therapy, as a hot field of tumor therapy, shows great potential and bright prospects, and is expected to bring good news to more tumor patients.
Reference：
1. Yu J, Upadhaya S, Tatake R, Barkalow F, Hubbard-Lucey V. Cancer cell therapies: The clinical trials landscape. Nature reviews Drug discovery, 2020, 19 (9) : 583-584.doi.org/10.1038/d41573-020-00099-9
2. Park J, Geyer M, Brentjens R. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: Interpreting clinical outcomes to date. "2016, 127 (26) : 3312-3320.doi.org/10.1182/blood-2016-02-629063
3. Lu J, Jiang G. The journey of CAR-T therapy in hematological malignancies. Molecular cancer 2022, 21(1): 194. doi.org/10.1186/s12943-022-01663-0
4. Cappell K, Kochenderfer J. A comparison of chimeric antigen receptors containing CD28 versus 4-1BB costimulatory domains. Nature Reviews Clinical oncology, 2021, 18 (11) : 715-727.doi.org/10.1038/s41571-021-00530-z
5. Valeri A, Garcia-Ortiz A, Castellano E, Cordoba L, Maroto-Martin E, Encinas J, et al. Overcoming tumor resistance mechanisms in CAR-NK cell therapy. Frontiers in immunology 2022, 13: 953849. doi.org/10.3389/fimmu.2022.953849
6. Nelson A, Lukacs J, Johnston B. The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead. Cancers 2021, 13 (20). Doi.org/10.3390/cancers13205174
7. Heczey A, Courtney A, Montalbano A, Robinson S, Liu K, Li M, et al. Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: An interim analysis. Nature medicine, 2020, 26 (11) : 1686-1690.doi.org/10.1038/s41591-020-1074-2
8. Chen Y, Yu Z, Tan X, Jiang H, Xu Z, Fang Y, et al. CAR-macrophage: A new immunotherapy candidate against solid tumors. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2021, 139:111605. doi.org/10.1016/j.biopha.2021.111605
9. Klichinsky M, Ruella M, Shestova O, Lu X, Best A, Zeeman M, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nature biotechnology 2020, 38(8): 947-953.doi.org/10.1038/s41587-020-0462-y
10. Zhao Q, Jiang Y, Xiang S, Kaboli P, Shen J, Zhao Y, et al. Engineered TCR-T Cell Immunotherapy in Anticancer Precision Medicine: Pros and Cons. The Frontiers in immunology 2021, 12:658753. doi.org/10.3389/fimmu.2021.658753
11. Ferreira M, Cabral E, Coroadinha A. Progress and Perspectives in the Development of Lentiviral Vector Producer Cells. Biotechnology journal 2021, 16 (1) : e2000017.doi.org/10.1002/biot.202000017
12. Wu X, He X, Liu F, Jiang X, Wang P, Zhang J, et al. ex vivoDevelopment and clinical translation of gene therapy. Computational and structural biotechnology journal 2022, 20:2986-3003.doi.org/10.1016/j.csbj.2022.06.015
13. Maalej K, Merhi M, Inchakalody V, Mestiri S, Alam M, Maccalli C, et al. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances. Molecular cancer 2023, 22(1): 20. doi.org/10.1186/s12943-023-01723-z
14. Baulu E, Gardet C, Chuvin N, Depil S. TCR-engineered T cell therapy in solid tumors: The State of the art and perspectives. The Science advances, 2023, 9 (7) : eadf3700.doi.org/10.1126/sciadv.adf3700
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 should not be used as a diagnosis or treatment, is not a substitute for professional medical advice, and the company's website will not assume any responsibility. The final interpretation of the content of the above statement belongs to the company's website, this statement will apply to the company's website all the time to share the article, thank you for your cooperation! Copyright description: The copyright of the article belongs to Shenzhen Cell Valley, individuals are welcome to forward to the circle of friends, media or institutions without authorization, reproduced in any form to other platforms, will be regarded as infringement. For reprinting, please contact email: contact@duanglink.com
Cell therapy refers to the transplantation or input of normal or bioengineered human cells into the patient, and the newly imported cells can replace the damaged cells, or have a stronger immune killing ability, so as to achieve the purpose of treating diseases. According to cell type, it can be divided into stem cell therapy and immune cell therapy. The stem cells used in clinical treatment mainly include bone marrow stem cells, hematopoietic stem cells, neural stem cells, skin stem cells, islet stem cells, fat stem cells and so on. Stem cell therapy uses the differentiation and repair principle of human stem cells to transplant healthy stem cells into the patient's body to repair diseased cells or rebuild normal functioning cells and tissues. Immune cell therapy is to collect immune cells from the human body, culture them in vitro, increase their number by thousands of times, or modify immune cells to make them become cells with enhanced targeted killing function, and then inject them back into the human body to kill pathogens, cancer cells, and mutant cells in the blood and tissues, break immune tolerance, and activate and enhance the body's immune capacity.
二、Immune cell therapy
(1)chimeric antigen receptor T-cell (CAR-T) : The fastest growing and most widely used branch of cellular immunotherapy. This latest technology is rapidly changing the landscape of hematological malignancies and accounts for more than half of all cell therapies currently in development or on the market [1, 2]. CAR-T refers to the transfer of genetic material with specific antigen recognition domain and T cell activation signal into T cells through gene modification technology, so that T cells can directly bind to the specific antigen on the tumor surface to achieve precise targeted therapy, which is a very promising tumor treatment [3]. The current mainstream technology is the second generation of CAR, and on the basis of the first generation, an immunoreceptor tyrosine-based activation motif from the co-stimulatory molecule CD28 or CD137 (4-1BB) is added into the cell. Therefore, the activation ability and killing activity of the second generation CAR is much stronger than that of the first generation, and it also shows a good therapeutic effect in clinical treatment. The third and fourth generation cars are all under development and are currently in the pre-clinical research stage, and their efficacy is worth expecting [4]. Although CAR-T cells have shown good results in the treatment of B-cell leukemia and lymphoma, there are currently six CAR-T drugs approved by the US Food and Drug Administration (FDA) and three CAR-T products approved by the State Drug Administration. Although CAR T cell drugs have shown great advantages in hematoma, they also have their own limitations, mainly manifested in poor treatment effect of solid tumor, relapse of drug resistance after treatment, and side effects in some patients. Researchers are also working to find novel target antigens, optimize CAR structure, and combine CAR-T with other therapies to further improve its efficacy.
(2)CAR-NK: Natural Killer (NK) cells are an important part of innate immunity in the body. Compared with T cells, NK cells have many advantages in the application of CAR. Allogeneic NK cells do not cause graft-versus-host disease (GVHD). NK cell therapy does not secrete inflammatory cytokines (IL-1, IL-6), and almost does not cause the occurrence of cytokine release syndrome. NK cells have more tumor killing pathways, such as performing cell degranulation, activating apoptosis pathways, and mediating antibody-dependent cell-mediated cytotoxic functions (ADCC). Allogeneic NK cells come from a wide range of sources, including peripheral blood, umbilical cord blood, NK cell line (NK92) and induced pluripotent stem cell (iPSC-NK). NK cells have a short survival cycle in vivo, which is different from CAR T cells, which have a long retention period and are prone to side effects and attack the patient's own cells. The treatment of solid tumors has obvious advantages, because solid tumors show varying degrees of tolerance to unmodified NK cells, but are sensitive to antigen-dependent NK cells. The above advantages make CAR-NK have great potential and broad prospect in tumor immunotherapy [5].
(3)CAR-NKT: Natural Killer-T (NKT) cells are congenital T lymphocytes. Unlike NK cells, the target recognition of NKT cells is restricted by CD1d, similar to the recognition target of T cells is restricted by HLA. Although most tumors are CD1D-negative and cannot be directly targeted by NKT cells, NKT cells migrate to tumor sites in response to tumor-derived chemokines, and in some tumor types, the presence of NKT cells in primary tumors is associated with a favorable prognosis. Within tumors, tumor-associated macrophages stimulate angiogenesis, promote tumor growth and invasion, and mediate immunosuppression, and NKT cells are capable of killing such cells. In addition, NKT cell activation can indirectly promote the anti-tumor response mediated by NK cells and T cells. Although the amount of NKT cells in the blood is small, based on the above advantages of NKT cells, it has great potential in the development of cancer cell therapy [6]. In the published interim phase 1 clinical data of CAR-NKT for neuroblastoma, 1 out of 3 patients who received the therapy achieved objective remission and bone metastases subsided [7].
(4)CAR-M: In the tumor microenvironment, macrophage is a native immune cell with the highest invasion rate and interacts with almost all cellular components in the tumor microenvironment including tumor cells, immune cells such as T cells, NK cells, DC and other resident non-immune cells [8]. The above characteristics have also generated great interest in the development of CAR-M. Macrophages are usually the first immune cells to be absorbed by solid tumors, and CAR can help macrophages accurately recognize tumor cells, avoid being absorbed, and in turn engulf tumor cells. CAR-M can also present cancer cell antigen fragments to T cells, activate T cells, and promote anti-cancer immunity [9]. At present, clinical trials of CAR-M are still in the research and development stage, and no results have been reported.
(5) T cell receptor T (TCR-T) : Tcr-t cell therapy introduces the tumor antigen-specific TCR gene screened in vitro into T cells in vitro by means of genetic engineering. By infusing TCR-T cells carrying exogenous TCR gene into patients, the anti-tumor immunity of the body can be reestablished, thus achieving the purpose of tumor treatment. Compared with CAR T cell therapy, TCR-T cell therapy has certain uniqueness. First, TCR can recruit the naturally occurring CD3 subunit in T cells to generate an immune response. CAR intracellular activation generally depends on the intracellular domain of CD3ζ, with 3 ITams, while the intracellular receptor domain of the TCR/CD3 complex has 10 ITams [10]. Secondly, the formation of immune synapses between TCR-T cells and target cells can recruit a variety of molecules to produce synergies. Third, TCR-T cells are more sensitive to antigen than CAR-T cells. Because TCR-T cell therapy has the unique advantage of targeting tumor intracellular antigens, it has become an important potential method for the treatment of solid tumors.
三、Selection of virus vector
The key of cell therapy is the design of gene transduction vector. The virus has the function of transmitting its genome into the recipient cell for infection, so it can be used as a delivery vector to bring the target gene into the target cell. Common viral vectors include retrovirus vector, lentiviral vector, adenovirus vector, adeno-associated virus and non-viral vector, among which retrovirus vector and lentiviral vector are the most widely used in cell therapy. Lentiviral vector is a single stranded RNA virus, which can randomly insert foreign fragments into the genome of host cells. Lentiviral vector has the advantages of short instantaneous transfection and packaging cycle, and can infect both dividing and non-dividing cells. Retroviral vector is a spherical virus with envelope, which also carries its genetic material in the form of RNA and randomly integrates into the genome of host cells. It can infect dividing cells, carry large gene fragments, and infect T cells, NK cells and other cells with high efficiency. In terms of industrial production, lentiviral vector adopts instantaneous packaging system, large amount of plasmids, complex purification process, and low titer of viral vector (requiring complex purification and concentration), while industrial production of retroviral vector can prepare stable virus-producing cell lines, less amount of plasmids, low impurity content, and high titer of viral vector. Due to the above advantages, the number of R&D pipelines using retroviral vectors in the field of cellular gene therapy has significantly exceeded the number of R&D pipelines using lentiviral vectors globally. At present, lentivirus vectors are mainly used in various R&D pipelines in China, and it is expected that retrovirus vectors will also be widely used in China in the future [11, 12].
At present, there are 9 CAR-T products on the market worldwide, of which 6 are using lentiviral vector technology and 3 are using retrovirus vector technology
| Product | Target | Listing year | Corporation | Vector |
| Kymriah | CD19；lymphoma | 2017.08.30 | Novartis | Lentivirus |
| Yescarta | CD19；lymphoma | 2017.10.18 | Kite | γRetrovirus |
| Tecartus | CD19；lymphoma、leukaemia | 2020.07 | Kite | Retroviral |
| Breyanzi | CD19；lymphoma | 2021.02.05 | Juno Therapeutics | Lentivirus |
| Abecma | BCMA；Myeloma | 2021.03 | BMS/Bluebird bio | Lentivirus |
| Akilensee injection (Ikaida) | CD19；lymphoma | 2021.06 | FOSUNKite （Introducing Yescarta） |
γRetrovirus |
| Rechiolencel Injection (Benoda) | CD19；lymphoma | 2021.09.03 | Jw (Cayman) Therapeutics Co. Ltd | Lentivirus |
| Carvykti (Sidagiorencel) | BCMA；Myeloma | 2022.02（FDA） | NASDAQ:LEGN | Lentivirus |
| Iquiolencel injection (Focoxol) | BCMA；Myeloma | 2023.06.30 | Reindeer Biology/ Xinda Biology |
Lentivirus |
四、Summary
With the market and application of CAR-T cell therapy, immune cell therapy has gradually played an irreplaceable role in tumor therapy relying on its unique advantages. CAR-NK cell therapy can overcome some limitations of CAR-T, such as graft-versus-host disease and cytokine release syndrome. CAR-NK therapy is a rising star of cell products due to its advantages such as reduced toxicity and easy preparation of general-purpose products. CAR-M cell therapy launches a multi-pronged attack on tumors by combining the innate immune system and the adaptive immune system [13]. Meanwhile, TCR-T cell therapy has shown very encouraging results in solid tumors [14]. In summary, immune cell therapy, as a hot field of tumor therapy, shows great potential and bright prospects, and is expected to bring good news to more tumor patients.
Reference：
1. Yu J, Upadhaya S, Tatake R, Barkalow F, Hubbard-Lucey V. Cancer cell therapies: The clinical trials landscape. Nature reviews Drug discovery, 2020, 19 (9) : 583-584.doi.org/10.1038/d41573-020-00099-9
2. Park J, Geyer M, Brentjens R. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: Interpreting clinical outcomes to date. "2016, 127 (26) : 3312-3320.doi.org/10.1182/blood-2016-02-629063
3. Lu J, Jiang G. The journey of CAR-T therapy in hematological malignancies. Molecular cancer 2022, 21(1): 194. doi.org/10.1186/s12943-022-01663-0
4. Cappell K, Kochenderfer J. A comparison of chimeric antigen receptors containing CD28 versus 4-1BB costimulatory domains. Nature Reviews Clinical oncology, 2021, 18 (11) : 715-727.doi.org/10.1038/s41571-021-00530-z
5. Valeri A, Garcia-Ortiz A, Castellano E, Cordoba L, Maroto-Martin E, Encinas J, et al. Overcoming tumor resistance mechanisms in CAR-NK cell therapy. Frontiers in immunology 2022, 13: 953849. doi.org/10.3389/fimmu.2022.953849
6. Nelson A, Lukacs J, Johnston B. The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead. Cancers 2021, 13 (20). Doi.org/10.3390/cancers13205174
7. Heczey A, Courtney A, Montalbano A, Robinson S, Liu K, Li M, et al. Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: An interim analysis. Nature medicine, 2020, 26 (11) : 1686-1690.doi.org/10.1038/s41591-020-1074-2
8. Chen Y, Yu Z, Tan X, Jiang H, Xu Z, Fang Y, et al. CAR-macrophage: A new immunotherapy candidate against solid tumors. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2021, 139:111605. doi.org/10.1016/j.biopha.2021.111605
9. Klichinsky M, Ruella M, Shestova O, Lu X, Best A, Zeeman M, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nature biotechnology 2020, 38(8): 947-953.doi.org/10.1038/s41587-020-0462-y
10. Zhao Q, Jiang Y, Xiang S, Kaboli P, Shen J, Zhao Y, et al. Engineered TCR-T Cell Immunotherapy in Anticancer Precision Medicine: Pros and Cons. The Frontiers in immunology 2021, 12:658753. doi.org/10.3389/fimmu.2021.658753
11. Ferreira M, Cabral E, Coroadinha A. Progress and Perspectives in the Development of Lentiviral Vector Producer Cells. Biotechnology journal 2021, 16 (1) : e2000017.doi.org/10.1002/biot.202000017
12. Wu X, He X, Liu F, Jiang X, Wang P, Zhang J, et al. ex vivoDevelopment and clinical translation of gene therapy. Computational and structural biotechnology journal 2022, 20:2986-3003.doi.org/10.1016/j.csbj.2022.06.015
13. Maalej K, Merhi M, Inchakalody V, Mestiri S, Alam M, Maccalli C, et al. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances. Molecular cancer 2023, 22(1): 20. doi.org/10.1186/s12943-023-01723-z
14. Baulu E, Gardet C, Chuvin N, Depil S. TCR-engineered T cell therapy in solid tumors: The State of the art and perspectives. The Science advances, 2023, 9 (7) : eadf3700.doi.org/10.1126/sciadv.adf3700
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 should not be used as a diagnosis or treatment, is not a substitute for professional medical advice, and the company's website will not assume any responsibility. The final interpretation of the content of the above statement belongs to the company's website, this statement will apply to the company's website all the time to share the article, thank you for your cooperation! Copyright description: The copyright of the article belongs to Shenzhen Cell Valley, individuals are welcome to forward to the circle of friends, media or institutions without authorization, reproduced in any form to other platforms, will be regarded as infringement. For reprinting, please contact email: contact@duanglink.com
