Research progress on CAR-T therapy for multiple myeloma
Multiple myeloma (MM) is a malignant proliferative tumor of plasma cells characterized by the abnormal accumulation of monoclonal plasma cells in the bone marrow and the production of monoclonal immunoglobulin or its fragments (M protein), thereby damaging related Organs and tissues, hypercalcemia, renal insufficiency, anemia and bone destruction are common clinical manifestations. In recent years, the incidence of MM has increased significantly worldwide, increasing by 126% from 1990 to 2016 [1], and now it has become the second most common malignant tumor in the blood system. Although proteasome inhibitors, immunomodulators, monoclonal antibodies and other drugs have made significant progress in the treatment of multiple myeloma, the emergence of recurrence and drug resistance is still a major challenge, and MM still cannot be completely cured. Therefore, the progress in research on CAR-T therapy for multiple myeloma is of great significance.
1、CAR-T therapy
CAR-T cell immunotherapy is a new type of treatment method that uses the patient's own immune system to fight cancer cells. Simply put, T cells collected from the patient's peripheral blood are isolated and used through gene transduction technology. The isolated T cells express CAR, and these cells are then infused back into the patient for anti-tumor treatment. CAR consists of four parts: a single-chain variable fragment (scFv) derived from a monoclonal antibody, a hinge region derived from CD8, a transmembrane domain, and an intracellular signaling domain (Figure 1). The first-generation CAR only contained an intracellular signaling domain, while the second-generation added costimulatory domains such as CD28 or 4-1BB to enhance the anti-tumor effect of CAR-T. The third generation further increased the costimulatory domain to two based on the second generation to promote the proliferation and activation of CAR-T. The fourth generation adds cytokines to the third generation to improve the killing power of CAR-T against tumors. Researchers have developed a new CAR construct. This new generation CD19 CAR encodes a truncated cytoplasmic domain from the interleukin (IL)-2 receptor beta chain (IL-2Rβ) and a STAT3-binding tyrosine- X-X-glutamine (YXXQ) motif, as well as TCR signaling (CD3ζ) and costimulatory (CD28) domains, this is considered a fifth-generation CAR[2], although this concept is currently in the exploratory stage, Compared with CAR-T cells expressing CD28 or 4-1BB costimulatory domains alone, this construct showed excellent in vivo persistence and anti-tumor effects in hematological tumors and solid tumor models, bringing new possibilities for the treatment of solid tumors. hope. After CAR-T is infused into the patient, it can specifically recognize and kill tumor cells expressing specific antigens through three pathways: cell lysis, cytokine release, and Fas/FasL, and is not affected by the major histocompatibility complex ( Maior histocompatibility complex (MHC) restrictions.
FIG. 2 MM therapeutic targets
FIG. 3 Schematic diagram of two-target CAR design
Compared with traditional treatments such as proteasome inhibitors, monoclonal antibodies, and immunomodulators, CAR-T cell therapy has more significant targeting and stronger killing capabilities, which improves the patient's degree of remission and survival. Continuous improvement. However, recurrence due to issues such as tumor cell immune evasion is still a huge challenge for researchers. At present, in response to this problem, clinical research on multi-target, especially dual-target CAR-T, has achieved initial results. It is believed that as more research and clinical trials are conducted, the safety and effectiveness of CAR-T cell therapy will be further improved, bringing more hope to patients with multiple myeloma.
At present, Shenzhen Cell Valley has won the bid for the "GMP-grade cell product production and preparation" project of Huazhong University of Science and Technology Union Shenzhen Hospital, providing it with the industrial preparation and clinical application of anti-BCMA CAR-T cell products based on retroviral vectors. What is gratifying is that the patient achieved very good partial remission one month after receiving CAR-T cell therapy. The patient has been discharged from the hospital for several months and has now reached complete remission (CR), and the M protein level has now dropped to 0 g/L! ! ! Interested readers are welcome to contact Shenzhen Cell Valley for in-depth exchanges!
Reference：
[1] VAN DE DONK N W C J, PAWLYN C, KL Y.Multiple mye-lomalJ. Lancet, 2021, 397(10272):410-427.
[2] Kagoya, Y.; Tanaka, S.; Guo, T.; Anczurowski, M.; Wang, C.H.; Saso, K.; Butler, M.O.; Minden, M.D.; Hirano, N. A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects. Nat. Med. 2018, 24, 352–359.
[3] NOOPUR RAJE M D J B. Anti-BCMA CAR T-Cell Therapybb2121 in Relapsed or Refractory Multiple Myeloma[J]. TheNew England Journal of Medicine, 2019(380) :1726-1737.
[4] LIN Y, MARTIN T, BERDEJA J G,et al. Ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in patients withrelapsed/refractory multiple myeloma: 2-year post LPI resultsfrom the phase 1b/2 CARTITUDE-1 study[J]. HemaSphere,2022, 6(Suppl) :851-852.
[5] Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target forthe treatment of multiple myeloma. Clin Cancer Res. 2008; 14 (9) : 2775-2784.
[6] Smith E L, Harrington K, Staehr M, et al. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells[J]. Science translational medicine, 2019, 11(485): eaau7746.
[7] SHAH N N, MAATMAN T, HARI P, et al. Multi TargetedCAR T Cell Therapies for B-Cell Malignancies[J]. Frontiers inOncology, 2019,9 :146.
[8] TAHMASEBI S, ELAHI R, KHOSH E,et al. Programmableand multi-targeted CARs: a new breakthrough in cancer CAR-Tcell therapy[J]. Clinical and Translational Oncology, 2021, 23(6):1003-1019.
[9] Xie, B.; Li, Z.; Zhou, J., Wang, W., Current status and perspectives of dual-targeting chimeric antigen receptor T-cell therapy for the treatment of hematological malignancies. Cancers 2022, 14.
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
1、CAR-T therapy
CAR-T cell immunotherapy is a new type of treatment method that uses the patient's own immune system to fight cancer cells. Simply put, T cells collected from the patient's peripheral blood are isolated and used through gene transduction technology. The isolated T cells express CAR, and these cells are then infused back into the patient for anti-tumor treatment. CAR consists of four parts: a single-chain variable fragment (scFv) derived from a monoclonal antibody, a hinge region derived from CD8, a transmembrane domain, and an intracellular signaling domain (Figure 1). The first-generation CAR only contained an intracellular signaling domain, while the second-generation added costimulatory domains such as CD28 or 4-1BB to enhance the anti-tumor effect of CAR-T. The third generation further increased the costimulatory domain to two based on the second generation to promote the proliferation and activation of CAR-T. The fourth generation adds cytokines to the third generation to improve the killing power of CAR-T against tumors. Researchers have developed a new CAR construct. This new generation CD19 CAR encodes a truncated cytoplasmic domain from the interleukin (IL)-2 receptor beta chain (IL-2Rβ) and a STAT3-binding tyrosine- X-X-glutamine (YXXQ) motif, as well as TCR signaling (CD3ζ) and costimulatory (CD28) domains, this is considered a fifth-generation CAR[2], although this concept is currently in the exploratory stage, Compared with CAR-T cells expressing CD28 or 4-1BB costimulatory domains alone, this construct showed excellent in vivo persistence and anti-tumor effects in hematological tumors and solid tumor models, bringing new possibilities for the treatment of solid tumors. hope. After CAR-T is infused into the patient, it can specifically recognize and kill tumor cells expressing specific antigens through three pathways: cell lysis, cytokine release, and Fas/FasL, and is not affected by the major histocompatibility complex ( Maior histocompatibility complex (MHC) restrictions.
Figure 1 Schematic diagram of CAR structure
2、MM CAR-T therapy targetCurrently, B cell maturation antigen (BCMA), signaling lymphocyte activation molecule family member F7 (SLAMF7), G protein-coupled receptor class C group 5 member D (G protein- coupled receptor class C group 5member D, GPRC5D), etc. have been used as targets for MM CAR-T therapy. Currently, a total of 3 CAR-T products targeting BCMA have been approved on the market. Among them, the BCMA CAR-T product bb2121 has been approved for marketing in March 2021, and another product cilta-cel has also been approved for marketing in February 2022. The latest product approved for marketing is Fukuda jointly developed by my country Reindeer/Innovent Biologics. Research on Kesu injection and several other antigens is also ongoing.
FIG. 2 MM therapeutic targets
01 BCMA
BCMA is a type III transmembrane protein that belongs to the tumor necrosis factor receptor (TNFR) family. Its expression is up-regulated at the end of B cell maturation, especially selectively expressed on plasma cells, and is highly expressed on most multiple myeloma cells. It is expressed horizontally, but is basically not expressed on naive B cells, memory B cells and other normal tissue cells. BCMA regulates the survival of long-lived plasma cells by binding to B cell activating factor (BAF) and activating the NF-KB and MAPK/JNK pathways. It can also promote MM in the bone marrow microenvironment by binding to proliferation-inducing ligand (APRIL). Cell proliferation.
bb2121 promoted by Bluebird Bio is a CAR-T product transduced by a lentiviral vector containing BCMA CAR. Raje et al. [3] reported a study of bb2121 in the treatment of relapsed/refractory multiple myeloma. A total of 36 patients with relapsed and refractory MM were enrolled, of whom 3 patients withdrew from the study due to disease before infusion. The overall response rate among 33 patients was 85%, with 45% having a complete response (9%) or a strict complete response (36%).
In addition, cilta-cel produced by Johnson & Johnson is another CAR-T product targeting BCMA. Unlike other anti-BCMA CAR-T therapies, it directly targets two BCMA epitopes (VH1 and VH2) to improve Affinity for BCMA-expressing cells. Researchers such as Lin [4] reported early, deep, and durable responses after infusion of cilta-cel in patients. A total of 97 patients participated in the study. The patients received a single infusion of 0.75×106/kg cilta-cel 5 to 7 days after clearing lymphoma. The ORR was 97.9% (95% CI: 92.7-99.7), of which 94.9% of the patients achieved VGPR, 82.5% of patients achieved sCR. Among 61 patients with uable bone marrow minimal residual disease (MRD), 92% of patients were MRD negative, and 44% of patients (27/61) were MRD negative for ≥6 months. The 2-year PFS rate of patients was 91%; 18% of patients remained MRD-negative for >12 months. Anti-BCMA CAR-T therapy has achieved satisfactory clinical efficacy in the treatment of MM, and RRMM patients can also benefit significantly from anti-BCMA CAR-T therapy. However, higher CRS and ICANS have also been observed with these products. Risks, how to further improve the safety and effectiveness of products is still a challenge that needs to be considered.
02 SLAMF7
SLAMF7, also known as CD319, CRACC, and CSSLAMF71, is a member of the signaling lymphocyte activation molecule (SLAM) family and plays an important role in regulating immune cell function. In normal tissues, the expression of SLAMF7 is restricted to the hematopoietic system, including NK cells, some T cells and B cells, monocytes, macrophages and dendritic cells. SLAMF7 is highly expressed in pre-B cells and plasma cells during the life cycle of normal B cells, and is highly expressed in malignant plasma cells in the stages of multiple myeloma, monoclonal gammopathy of unknown significance, and smoldering myeloma. horizontal expression. Studies have shown that SLAMF7 is uniformly expressed on malignant plasma cells of newly diagnosed (ND) myeloma, and expression is still retained in relapsed myeloma after intensive radiotherapy and chemotherapy [5]. It is not known in other normal human tissues. The discovery of SLAMF7 expression makes SLAMF7 a potential target in CAR T cell therapy for myeloma.
03 GPRC5D
GPRC5D is a transmembrane receptor protein that is mainly expressed on the surface of plasma cells. Compared with normal cells, the expression level of GPRC5D in multiple myeloma (MM) cells is significantly increased, so it is considered a potential therapeutic target for MM. One of the points. Immunohistochemistry shows that GPRC5D is ubiquitously expressed on malignant myeloma cells, with similar but independent distribution to BCMA, and its expression in normal tissues is limited to hair follicles. Based on this, some researchers designed a CAR-T [6] containing seven human scFvs targeting GPRC5D, which can eradicate MM cells in xenograft MM mouse models and enable mice to achieve long-term survival. 100 days after injection of GPRC5D-CAR-T, the mice maintained 100% survival rate and did not suffer side effects such as hair loss or skin damage. This finding provides important preclinical evidence for GPRC5D as an important clinical target for MM immunotherapy.
3、Dual-target CAR-T
Although MM patients have a good initial response after receiving CAR-T treatment, clinical studies have found that the proportion of patients relapse due to antigen escape is also high. This may be related to the insufficient expansion and persistence of CAR-T cells in the body and the loss of tumor-associated antigens. or down-regulation, as well as the presence of immunosuppressive factors in the tumor microenvironment. Due to limited existing treatments, the prognosis for most patients with recurrence is poor. The development of multi-target CAR-T for multiple antigen receptors is considered to be the most significant solution to the problem of antigen escape, especially the development of dual-target CAR-T, such as the clinical trial of BCMA/CD19 dual-target CAR-T. development.
Theoretically, bispecific CAR-T cells can be achieved in the following four ways [7-9]: 1) As shown in 3A, Cocktail/Sequential infusion, that is, monospecific CAR-T cell combination therapy (that is, cocktail therapy). The disadvantage of this combination therapy is that the expansion rates of two different target CAR-T cells in the body are different, which will eventually lead to an imbalance in the ratio of the two CAR-T cells and cannot better eliminate tumor cells; 2) As shown in the figure 3B, Co-transduction, that is, two viral vectors each encode a monospecific CAR molecule, and then the two viruses are co-transduced into T cells to form bispecific CAR-T cells. However, due to differences in transduction efficiency, the ratio of the two CAR molecules on the CAR-T cells formed by this method is unbalanced, and there may also be situations where only one CAR molecule is expressed on the T cells; 3) Figure 3C , Bicistronic CAR-T cells use a viral vector to encode two monospecific CAR molecules, so that there are two CAR molecules on the CAR-T cells. The bispecific CAR-T cells constructed by this method can target two antigens and the ratio of the two CAR molecules is equal. However, the disadvantage of this method is that the viral vector load is limited. The efficiency of the virus encoding two CAR molecules at the same time is low, resulting in a low expression of CAR molecules on CAR-T cells and the expression of the second CAR molecule may be incomplete; 4) As shown in Figure 3D-E, Bivalent CAR-T cells, That is, a virus encodes a CAR molecule, and this CAR molecule contains two antigen-binding sites. The structure of Bivalent CAR-T cells can be divided into two forms: linear tandem (Tandem) or loop (Loop) configuration. These two bivalent CARs are currently the most researched and widely used bispecific CAR-T cell configurations.
BCMA is a type III transmembrane protein that belongs to the tumor necrosis factor receptor (TNFR) family. Its expression is up-regulated at the end of B cell maturation, especially selectively expressed on plasma cells, and is highly expressed on most multiple myeloma cells. It is expressed horizontally, but is basically not expressed on naive B cells, memory B cells and other normal tissue cells. BCMA regulates the survival of long-lived plasma cells by binding to B cell activating factor (BAF) and activating the NF-KB and MAPK/JNK pathways. It can also promote MM in the bone marrow microenvironment by binding to proliferation-inducing ligand (APRIL). Cell proliferation.
bb2121 promoted by Bluebird Bio is a CAR-T product transduced by a lentiviral vector containing BCMA CAR. Raje et al. [3] reported a study of bb2121 in the treatment of relapsed/refractory multiple myeloma. A total of 36 patients with relapsed and refractory MM were enrolled, of whom 3 patients withdrew from the study due to disease before infusion. The overall response rate among 33 patients was 85%, with 45% having a complete response (9%) or a strict complete response (36%).
In addition, cilta-cel produced by Johnson & Johnson is another CAR-T product targeting BCMA. Unlike other anti-BCMA CAR-T therapies, it directly targets two BCMA epitopes (VH1 and VH2) to improve Affinity for BCMA-expressing cells. Researchers such as Lin [4] reported early, deep, and durable responses after infusion of cilta-cel in patients. A total of 97 patients participated in the study. The patients received a single infusion of 0.75×106/kg cilta-cel 5 to 7 days after clearing lymphoma. The ORR was 97.9% (95% CI: 92.7-99.7), of which 94.9% of the patients achieved VGPR, 82.5% of patients achieved sCR. Among 61 patients with uable bone marrow minimal residual disease (MRD), 92% of patients were MRD negative, and 44% of patients (27/61) were MRD negative for ≥6 months. The 2-year PFS rate of patients was 91%; 18% of patients remained MRD-negative for >12 months. Anti-BCMA CAR-T therapy has achieved satisfactory clinical efficacy in the treatment of MM, and RRMM patients can also benefit significantly from anti-BCMA CAR-T therapy. However, higher CRS and ICANS have also been observed with these products. Risks, how to further improve the safety and effectiveness of products is still a challenge that needs to be considered.
02 SLAMF7
SLAMF7, also known as CD319, CRACC, and CSSLAMF71, is a member of the signaling lymphocyte activation molecule (SLAM) family and plays an important role in regulating immune cell function. In normal tissues, the expression of SLAMF7 is restricted to the hematopoietic system, including NK cells, some T cells and B cells, monocytes, macrophages and dendritic cells. SLAMF7 is highly expressed in pre-B cells and plasma cells during the life cycle of normal B cells, and is highly expressed in malignant plasma cells in the stages of multiple myeloma, monoclonal gammopathy of unknown significance, and smoldering myeloma. horizontal expression. Studies have shown that SLAMF7 is uniformly expressed on malignant plasma cells of newly diagnosed (ND) myeloma, and expression is still retained in relapsed myeloma after intensive radiotherapy and chemotherapy [5]. It is not known in other normal human tissues. The discovery of SLAMF7 expression makes SLAMF7 a potential target in CAR T cell therapy for myeloma.
03 GPRC5D
GPRC5D is a transmembrane receptor protein that is mainly expressed on the surface of plasma cells. Compared with normal cells, the expression level of GPRC5D in multiple myeloma (MM) cells is significantly increased, so it is considered a potential therapeutic target for MM. One of the points. Immunohistochemistry shows that GPRC5D is ubiquitously expressed on malignant myeloma cells, with similar but independent distribution to BCMA, and its expression in normal tissues is limited to hair follicles. Based on this, some researchers designed a CAR-T [6] containing seven human scFvs targeting GPRC5D, which can eradicate MM cells in xenograft MM mouse models and enable mice to achieve long-term survival. 100 days after injection of GPRC5D-CAR-T, the mice maintained 100% survival rate and did not suffer side effects such as hair loss or skin damage. This finding provides important preclinical evidence for GPRC5D as an important clinical target for MM immunotherapy.
3、Dual-target CAR-T
Although MM patients have a good initial response after receiving CAR-T treatment, clinical studies have found that the proportion of patients relapse due to antigen escape is also high. This may be related to the insufficient expansion and persistence of CAR-T cells in the body and the loss of tumor-associated antigens. or down-regulation, as well as the presence of immunosuppressive factors in the tumor microenvironment. Due to limited existing treatments, the prognosis for most patients with recurrence is poor. The development of multi-target CAR-T for multiple antigen receptors is considered to be the most significant solution to the problem of antigen escape, especially the development of dual-target CAR-T, such as the clinical trial of BCMA/CD19 dual-target CAR-T. development.
Theoretically, bispecific CAR-T cells can be achieved in the following four ways [7-9]: 1) As shown in 3A, Cocktail/Sequential infusion, that is, monospecific CAR-T cell combination therapy (that is, cocktail therapy). The disadvantage of this combination therapy is that the expansion rates of two different target CAR-T cells in the body are different, which will eventually lead to an imbalance in the ratio of the two CAR-T cells and cannot better eliminate tumor cells; 2) As shown in the figure 3B, Co-transduction, that is, two viral vectors each encode a monospecific CAR molecule, and then the two viruses are co-transduced into T cells to form bispecific CAR-T cells. However, due to differences in transduction efficiency, the ratio of the two CAR molecules on the CAR-T cells formed by this method is unbalanced, and there may also be situations where only one CAR molecule is expressed on the T cells; 3) Figure 3C , Bicistronic CAR-T cells use a viral vector to encode two monospecific CAR molecules, so that there are two CAR molecules on the CAR-T cells. The bispecific CAR-T cells constructed by this method can target two antigens and the ratio of the two CAR molecules is equal. However, the disadvantage of this method is that the viral vector load is limited. The efficiency of the virus encoding two CAR molecules at the same time is low, resulting in a low expression of CAR molecules on CAR-T cells and the expression of the second CAR molecule may be incomplete; 4) As shown in Figure 3D-E, Bivalent CAR-T cells, That is, a virus encodes a CAR molecule, and this CAR molecule contains two antigen-binding sites. The structure of Bivalent CAR-T cells can be divided into two forms: linear tandem (Tandem) or loop (Loop) configuration. These two bivalent CARs are currently the most researched and widely used bispecific CAR-T cell configurations.
FIG. 3 Schematic diagram of two-target CAR design
Compared with traditional treatments such as proteasome inhibitors, monoclonal antibodies, and immunomodulators, CAR-T cell therapy has more significant targeting and stronger killing capabilities, which improves the patient's degree of remission and survival. Continuous improvement. However, recurrence due to issues such as tumor cell immune evasion is still a huge challenge for researchers. At present, in response to this problem, clinical research on multi-target, especially dual-target CAR-T, has achieved initial results. It is believed that as more research and clinical trials are conducted, the safety and effectiveness of CAR-T cell therapy will be further improved, bringing more hope to patients with multiple myeloma.
At present, Shenzhen Cell Valley has won the bid for the "GMP-grade cell product production and preparation" project of Huazhong University of Science and Technology Union Shenzhen Hospital, providing it with the industrial preparation and clinical application of anti-BCMA CAR-T cell products based on retroviral vectors. What is gratifying is that the patient achieved very good partial remission one month after receiving CAR-T cell therapy. The patient has been discharged from the hospital for several months and has now reached complete remission (CR), and the M protein level has now dropped to 0 g/L! ! ! Interested readers are welcome to contact Shenzhen Cell Valley for in-depth exchanges!
Reference：
[1] VAN DE DONK N W C J, PAWLYN C, KL Y.Multiple mye-lomalJ. Lancet, 2021, 397(10272):410-427.
[2] Kagoya, Y.; Tanaka, S.; Guo, T.; Anczurowski, M.; Wang, C.H.; Saso, K.; Butler, M.O.; Minden, M.D.; Hirano, N. A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects. Nat. Med. 2018, 24, 352–359.
[3] NOOPUR RAJE M D J B. Anti-BCMA CAR T-Cell Therapybb2121 in Relapsed or Refractory Multiple Myeloma[J]. TheNew England Journal of Medicine, 2019(380) :1726-1737.
[4] LIN Y, MARTIN T, BERDEJA J G,et al. Ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in patients withrelapsed/refractory multiple myeloma: 2-year post LPI resultsfrom the phase 1b/2 CARTITUDE-1 study[J]. HemaSphere,2022, 6(Suppl) :851-852.
[5] Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target forthe treatment of multiple myeloma. Clin Cancer Res. 2008; 14 (9) : 2775-2784.
[6] Smith E L, Harrington K, Staehr M, et al. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells[J]. Science translational medicine, 2019, 11(485): eaau7746.
[7] SHAH N N, MAATMAN T, HARI P, et al. Multi TargetedCAR T Cell Therapies for B-Cell Malignancies[J]. Frontiers inOncology, 2019,9 :146.
[8] TAHMASEBI S, ELAHI R, KHOSH E,et al. Programmableand multi-targeted CARs: a new breakthrough in cancer CAR-Tcell therapy[J]. Clinical and Translational Oncology, 2021, 23(6):1003-1019.
[9] Xie, B.; Li, Z.; Zhou, J., Wang, W., Current status and perspectives of dual-targeting chimeric antigen receptor T-cell therapy for the treatment of hematological malignancies. Cancers 2022, 14.
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
