Current status of cell therapy research
1、Overview of cell therapy
Cell therapy refers to the transplantation or infusion of normal or bioengineered human cells into patients. The newly imported cells can replace damaged cells or have stronger immune killing capabilities, thereby achieving the purpose of treating diseases. According to cell type, it can be divided into stem cell therapy and immune cell therapy. The types of stem cells used for clinical treatment mainly include bone marrow stem cells, hematopoietic stem cells, neural stem cells, skin stem cells, pancreatic islet stem cells, adipose stem cells, etc. Stem cell therapy uses the differentiation and repair principles 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 and culture them in vitro to increase the number thousands of times, or to modify the immune cells to become cells with enhanced targeted killing function, and then infuse them back into the human body for killing. Pathogens, cancer cells, and mutated cells in the blood and tissues break immune tolerance and activate and enhance the body's immune capabilities.
2、Immune cell therapy
Immune cell therapy can be divided into the following types according to the different types of modified immune cells:
(1)Chimeric antigen receptor T-cell (CAR-T): the fastest growing and most widely used branch of cellular immunotherapy. This latest technology has rapidly changed the landscape of hematological malignancies and accounts for more than half of the cell therapies currently in development or on the market [1, 2]. CAR-T refers to the use of genetic modification technology to transfer genetic material with specific antigen recognition domains and T cell activation signals into T cells, allowing T cells to directly bind to specific antigens on the tumor surface to achieve precise targeting. treatment is a promising method of cancer treatment [3]. The current mainstream technology is the second generation CAR. 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. motif, ITAM) region, so the activation ability and killing activity of the second-generation CAR are much stronger than those of the first-generation CAR, and it also shows better therapeutic effects in clinical treatment. The third and fourth generations of CAR are all under development and are currently in the preclinical research stage, and their efficacy is worth looking forward to [4]. Although CAR-T cells have shown good results in the treatment of B-cell leukemia and lymphoma, there are currently 6 CAR-T drugs approved for marketing by the U.S. Food and Drug Administration (FDA), and 3 CAR-T products have been approved by the National The Drug Administration has approved marketing; although CAR-T cell drugs have shown great advantages in hematological tumors, they also have their own limitations, mainly manifested in poor treatment effects of solid tumors, drug-resistant relapse after treatment, and some patients side effects. Researchers are also working on finding new target antigens, optimizing CAR structures, and combining CAR-T with other treatments to further improve its efficacy.
(2)CAR-NK: Natural Killer (NK) cells are an important part of the body's innate immunity. Compared with T cells, NK cells have many advantages in the application of CAR. Allogeneic NK cells will not cause graft-versus-host disease (GVHD); NK cell therapy does not secrete inflammatory factors (IL-1, IL-6) and will rarely lead to the occurrence of cytokine release syndrome; NK cells have more Tumor killing pathways, such as executing cell degranulation, activating apoptotic pathways and mediating antibody-dependent cell-mediated cytotoxicity (ADCC); allogeneic NK cells come from a wide range of sources, including peripheral blood, umbilical cord blood, NK cell lines (NK92) and induction Pluripotent stem cells (iPSC-NK), etc.; NK cells have a short survival period in the body, unlike CAR-T cells, which have a long retention period and are prone to side effects and attack the patient's own cells; they have obvious advantages in the treatment of solid tumors, because solid tumors are resistant to non-modified cells. NK cells will show varying degrees of tolerance, but are sensitive to antigen-dependent NK cells. The above advantages make CAR-NK have great potential and broad prospects in tumor immunotherapy [5].
(3)CAR-NKT: Natural Killer-T (NKT) cells are innate T lymphocytes. Unlike NK cells, the target recognition of NKT cells is restricted by CD1d, similar to the target recognition of T cells that is restricted by HLA. Although most tumors are CD1d negative and cannot be directly targeted by NKT cells, NKT cells can migrate to the tumor site in response to tumor-derived chemokines, and in some types of tumors, the presence of NKT cells in the primary tumor associated with good prognosis. Within tumors, tumor-associated macrophages stimulate angiogenesis, promote tumor growth and invasion, and mediate immunosuppression, and NKT cells can kill these cells. In addition, NKT cell activation can indirectly promote NK cell- and T-cell-mediated anti-tumor responses. Although the content of NKT cells in the blood is small, based on the advantages of NKT cells, they have great potential in the development of cancer cell therapy [6]. In the published interim clinical data of the phase 1 clinical trial of CAR-NKT in the treatment of neuroblastoma, 1 of 3 patients who received this therapy achieved objective response, and the bone metastases disappeared [7].
(4)CAR-M: In the tumor microenvironment, macrophages are the natural immune cells with the highest infiltration rate, and interact with almost all cellular components in the tumor microenvironment (including tumor cells, immune cells such as T cells, NK cells, DCs and other resident non-immune cells) interact [8]. The above characteristics have made researchers very interested in the development of CAR-M. Macrophages are usually the first immune cells to be absorbed by solid tumors. CAR can help macrophages accurately identify tumor cells, avoid the fate of being absorbed, and in turn phagocytose tumor cells. CAR-M can also present cancer cell antigen fragments to T cells, activate T cells, and promote anti-cancer immunity [9]. Currently, clinical trials of CAR-M are still in the research and development stage, and no results have been reported yet.
(5)T cell receptor T cells (T cell receptor-T, TCR-T): TCR-T cell therapy introduces the tumor antigen-specific TCR genes screened in vitro into isolated T cells through genetic engineering means. Patients are infused with TCR-T cells carrying exogenous TCR genes to reconstruct the body's anti-tumor immunity, thereby 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 subunits in T cells to generate an immune response. The intracellular activation of CAR generally relies on the intracellular domain of CD3ζ, which has three ITAMs, and the intracellular receptor domain of the TCR/CD3 complex There are 10 ITAMs[10]. Secondly, the immune synapse formed between TCR-T cells and target cells can recruit a variety of molecules to produce synergistic effects. Third, TCR-T cells are more sensitive to antigens 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.
3、Selection of virus vector
The key to cell therapy is the design of gene transduction vectors. Viruses have the function of transmitting their genome into recipient cells for infection, and therefore can be used as delivery vectors to bring genes of interest into target cells. Common viral vectors include retroviral vectors, lentiviral vectors, adenoviral vectors, adeno-associated viruses and non-viral vectors, among which retroviral vectors and lentiviral vectors are the most widely used in cell therapy. Lentiviral vectors are single-stranded RNA viruses that can randomly insert exogenous fragments into the genome of host cells. Lentiviral vectors have the advantages of short transient transfection and packaging cycles, and can infect dividing and non-dividing cells. Retroviral vector is an enveloped spherical virus that also carries its genetic material in the form of RNA and is randomly integrated into the genome of the host cell. It can infect dividing cells and can carry larger gene fragments and infect T cells, NK and other cells are highly efficient. In terms of industrial production, lentiviral vectors use a transient packaging system, require a large amount of plasmid, have a complex purification process, and have low viral vector titers (requiring complex purification and concentration), while industrial production of retroviral vectors can prepare stable toxin-producing cell lines, The plasmid dosage is small, the impurity content is low, and the viral vector titer is high. Due to the above advantages, globally, the number of R&D pipelines using retroviral vectors in the field of cell gene therapy has greatly exceeded the number of R&D pipelines using lentiviral vectors. China's current various R&D pipelines mainly use lentiviral vectors, and it is expected that retroviral 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
4、Summary
With the launch and application of CAR-T cell therapy, immune cell therapy has gradually played an irreplaceable role in tumor treatment 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 in cell products due to its advantages such as reduced toxicity and easy preparation of universal 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 popular field of tumor treatment, 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 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@sz-cell.com
Cell therapy refers to the transplantation or infusion of normal or bioengineered human cells into patients. The newly imported cells can replace damaged cells or have stronger immune killing capabilities, thereby achieving the purpose of treating diseases. According to cell type, it can be divided into stem cell therapy and immune cell therapy. The types of stem cells used for clinical treatment mainly include bone marrow stem cells, hematopoietic stem cells, neural stem cells, skin stem cells, pancreatic islet stem cells, adipose stem cells, etc. Stem cell therapy uses the differentiation and repair principles 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 and culture them in vitro to increase the number thousands of times, or to modify the immune cells to become cells with enhanced targeted killing function, and then infuse them back into the human body for killing. Pathogens, cancer cells, and mutated cells in the blood and tissues break immune tolerance and activate and enhance the body's immune capabilities.
2、Immune cell therapy
Immune cell therapy can be divided into the following types according to the different types of modified immune cells:
(1)Chimeric antigen receptor T-cell (CAR-T): the fastest growing and most widely used branch of cellular immunotherapy. This latest technology has rapidly changed the landscape of hematological malignancies and accounts for more than half of the cell therapies currently in development or on the market [1, 2]. CAR-T refers to the use of genetic modification technology to transfer genetic material with specific antigen recognition domains and T cell activation signals into T cells, allowing T cells to directly bind to specific antigens on the tumor surface to achieve precise targeting. treatment is a promising method of cancer treatment [3]. The current mainstream technology is the second generation CAR. 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. motif, ITAM) region, so the activation ability and killing activity of the second-generation CAR are much stronger than those of the first-generation CAR, and it also shows better therapeutic effects in clinical treatment. The third and fourth generations of CAR are all under development and are currently in the preclinical research stage, and their efficacy is worth looking forward to [4]. Although CAR-T cells have shown good results in the treatment of B-cell leukemia and lymphoma, there are currently 6 CAR-T drugs approved for marketing by the U.S. Food and Drug Administration (FDA), and 3 CAR-T products have been approved by the National The Drug Administration has approved marketing; although CAR-T cell drugs have shown great advantages in hematological tumors, they also have their own limitations, mainly manifested in poor treatment effects of solid tumors, drug-resistant relapse after treatment, and some patients side effects. Researchers are also working on finding new target antigens, optimizing CAR structures, and combining CAR-T with other treatments to further improve its efficacy.
(2)CAR-NK: Natural Killer (NK) cells are an important part of the body's innate immunity. Compared with T cells, NK cells have many advantages in the application of CAR. Allogeneic NK cells will not cause graft-versus-host disease (GVHD); NK cell therapy does not secrete inflammatory factors (IL-1, IL-6) and will rarely lead to the occurrence of cytokine release syndrome; NK cells have more Tumor killing pathways, such as executing cell degranulation, activating apoptotic pathways and mediating antibody-dependent cell-mediated cytotoxicity (ADCC); allogeneic NK cells come from a wide range of sources, including peripheral blood, umbilical cord blood, NK cell lines (NK92) and induction Pluripotent stem cells (iPSC-NK), etc.; NK cells have a short survival period in the body, unlike CAR-T cells, which have a long retention period and are prone to side effects and attack the patient's own cells; they have obvious advantages in the treatment of solid tumors, because solid tumors are resistant to non-modified cells. NK cells will show varying degrees of tolerance, but are sensitive to antigen-dependent NK cells. The above advantages make CAR-NK have great potential and broad prospects in tumor immunotherapy [5].
(3)CAR-NKT: Natural Killer-T (NKT) cells are innate T lymphocytes. Unlike NK cells, the target recognition of NKT cells is restricted by CD1d, similar to the target recognition of T cells that is restricted by HLA. Although most tumors are CD1d negative and cannot be directly targeted by NKT cells, NKT cells can migrate to the tumor site in response to tumor-derived chemokines, and in some types of tumors, the presence of NKT cells in the primary tumor associated with good prognosis. Within tumors, tumor-associated macrophages stimulate angiogenesis, promote tumor growth and invasion, and mediate immunosuppression, and NKT cells can kill these cells. In addition, NKT cell activation can indirectly promote NK cell- and T-cell-mediated anti-tumor responses. Although the content of NKT cells in the blood is small, based on the advantages of NKT cells, they have great potential in the development of cancer cell therapy [6]. In the published interim clinical data of the phase 1 clinical trial of CAR-NKT in the treatment of neuroblastoma, 1 of 3 patients who received this therapy achieved objective response, and the bone metastases disappeared [7].
(4)CAR-M: In the tumor microenvironment, macrophages are the natural immune cells with the highest infiltration rate, and interact with almost all cellular components in the tumor microenvironment (including tumor cells, immune cells such as T cells, NK cells, DCs and other resident non-immune cells) interact [8]. The above characteristics have made researchers very interested in the development of CAR-M. Macrophages are usually the first immune cells to be absorbed by solid tumors. CAR can help macrophages accurately identify tumor cells, avoid the fate of being absorbed, and in turn phagocytose tumor cells. CAR-M can also present cancer cell antigen fragments to T cells, activate T cells, and promote anti-cancer immunity [9]. Currently, clinical trials of CAR-M are still in the research and development stage, and no results have been reported yet.
(5)T cell receptor T cells (T cell receptor-T, TCR-T): TCR-T cell therapy introduces the tumor antigen-specific TCR genes screened in vitro into isolated T cells through genetic engineering means. Patients are infused with TCR-T cells carrying exogenous TCR genes to reconstruct the body's anti-tumor immunity, thereby 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 subunits in T cells to generate an immune response. The intracellular activation of CAR generally relies on the intracellular domain of CD3ζ, which has three ITAMs, and the intracellular receptor domain of the TCR/CD3 complex There are 10 ITAMs[10]. Secondly, the immune synapse formed between TCR-T cells and target cells can recruit a variety of molecules to produce synergistic effects. Third, TCR-T cells are more sensitive to antigens 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.
3、Selection of virus vector
The key to cell therapy is the design of gene transduction vectors. Viruses have the function of transmitting their genome into recipient cells for infection, and therefore can be used as delivery vectors to bring genes of interest into target cells. Common viral vectors include retroviral vectors, lentiviral vectors, adenoviral vectors, adeno-associated viruses and non-viral vectors, among which retroviral vectors and lentiviral vectors are the most widely used in cell therapy. Lentiviral vectors are single-stranded RNA viruses that can randomly insert exogenous fragments into the genome of host cells. Lentiviral vectors have the advantages of short transient transfection and packaging cycles, and can infect dividing and non-dividing cells. Retroviral vector is an enveloped spherical virus that also carries its genetic material in the form of RNA and is randomly integrated into the genome of the host cell. It can infect dividing cells and can carry larger gene fragments and infect T cells, NK and other cells are highly efficient. In terms of industrial production, lentiviral vectors use a transient packaging system, require a large amount of plasmid, have a complex purification process, and have low viral vector titers (requiring complex purification and concentration), while industrial production of retroviral vectors can prepare stable toxin-producing cell lines, The plasmid dosage is small, the impurity content is low, and the viral vector titer is high. Due to the above advantages, globally, the number of R&D pipelines using retroviral vectors in the field of cell gene therapy has greatly exceeded the number of R&D pipelines using lentiviral vectors. China's current various R&D pipelines mainly use lentiviral vectors, and it is expected that retroviral 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 |
4、Summary
With the launch and application of CAR-T cell therapy, immune cell therapy has gradually played an irreplaceable role in tumor treatment 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 in cell products due to its advantages such as reduced toxicity and easy preparation of universal 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 popular field of tumor treatment, 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 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@sz-cell.com
