CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond
Abstract
:1. Introduction
2. Components of CAR-T-Cell Therapy and the Emergence of a Different Generation of CARs
2.1. First-Generation CAR T Cells
2.2. Second-Generation CAR T Cells
2.3. Third-Generation CAR T Cells
2.4. Fourth-Generation CAR T Cells
2.5. Next or Fifth-Generation CAR T Cells
3. Emergence of B-Cell Maturation Antigen (BCMA) as a Promising Target for CAR-T-Cell Therapy in Multiple Myeloma
3.1. Structure and Interaction of BCMA
3.2. Idecabtagene Vicleucel (Ide-Cel, bb2121)
3.3. Ciltacabtagene Autoleucel
3.4. JCARH125 (Orva-Cel)
3.5. JNJ-4528 (LCAR-B38M)
4. Non-BCMA CAR-T-Cell Targets
4.1. GPRC5D
4.2. SLAMF7/CS1
4.3. CD38
4.4. CD19
4.5. CD138
4.6. NKG2D
5. Limitations of CAR-T-Cell Therapy in Multiple Myeloma
5.1. On-Target, Off-Tumor
5.2. Cytokine Release Syndrome
5.3. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
5.4. Immunosuppressive Microenvironment
6. Recent Advances in BCMA Bispecific Antibodies
6.1. Comparison with BCMA CAR-T Therapy
6.2. Potential Synergies and Complementary Roles
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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(A) BCMA Targeted CAR-T for MM | |||||
Clinical Trial Name | Antigen Target | CAR Name | Sponsor | Phase | Current Status |
NCT05393804 | BCMA | Idecabtagene Vicleucel (ide-cel, bb2121) | Memorial Sloan Kettering Cancer Cente | 2 | Recruiting |
NCT05347485 | BCMA | Ciltacabtagene Autoleucel | Janssen Scientific Affairs, LLC | 2 | Recruiting |
NCT04181827 | BCMA | JCARH125 | Janseen Research & Development | 3 | Active/Non-recruiting |
NCT03090659 | BCMA | LEGEND-2 | Nanjing Legend Biotech Co. Second Affiliated Hospital of Xi’an Jiaotong University Ruijin Hospital Jiangsu Provincial People’s Hospital Shanghai Changzheng Hospital | 1/2 | Active, not recruiting |
NCT03548207 | BCMA | CARTITUDE-1 | Janssen Research & Development, LLC | 1/2 | Completed |
NCT02954445 | BCMA | NA | Shiqi Li, Southwest Hospital, China (Responsible Party) Southwest Hospital, China | 1/2 | Unknown |
NCT05860036 | BCMA | NA | Institute of Hematology & Blood Diseases Hospital Gang An, Institute of Hematology & Blood Diseases Hospital (Responsible Party) | 1 | Recruiting |
NCT05740891 | BCMA | NA | Zhejiang University He Huang, Zhejiang University | 1 | Recruiting |
NCT03716856 | BCMA | NA | First Affiliated Hospital of Zhejiang University | 1 | Unknown |
NCT05594797 | BCMA | NA | Hrain Biotechnology Co., Ltd. | 2 | Recruiting |
NCT04003168 | BCMA | NA | Hrain Biotechnology Co., Ltd. | 1 | Recruiting |
NCT03338972 | BCMA | NA | Fred Hutchinson Cancer Center | 1 | Completed |
NCT04727008 | BCMA | CXCR4 | Sichuan University Ting Niu, West China Hospital | Early Phase 1 | Not Yet Recruiting |
NCT05698303 | BCMA | NA | Nanjing IASO Biotherapeutics Co., Ltd. | 1 | Not Yet Recruiting |
NCT04637269 | Xinqiao Hospital of Chongqing Xi Zhang, MD, Xinqiao Hospital of Chongqing | Early Phase 1 | Recruiting | ||
NCT04322292 | BCMA | C-CAR088 | Institute of Hematology & Blood Diseases Hospital AnGang, Institute of Hematology & Blood Diseases Hospital | 1 | Unknown |
(B) Non-BCMA Targeted CAR-T for MM | |||||
Clinical Trial Name | Antigen Target | CAR Name | Sponsor | Phase | Current Status |
NCT04674813 | GPRC5D | CC-95266 | Juno Therapeutics, a Subsidiary of Celgene | 1 | Active, Recruiting |
NCT05016778 | GPRC5D | POLARIS | Zhejiang University & OriCell Therapeutics Co., Ltd. | Early Phase 1 | Active, not recruiting |
NCT05431608 | GPRC5D | NA | Memorial Sloan Kettering Cancer Center | 1 | Active, Recruiting |
NCT05325801 | GPRC5D & BCMA | OriC321 | Zhejiang University | 1 | Recruiting |
NCT05509530 | GPRC5D & BCMA | NA | Xuzhou Medical University | 2 | Recruiting |
NCT03958656 | SLAMF7 | NA | National Cancer Institute (NCI) | 1 | Completed |
NCT03710421 | CS1 | NA | City of Hope Medical Center | 1 | Active, Recruiting |
NCT04499339 | SLAMF7 | CARAMBA-1 | European Commission and Wuerzburg University Hospital | 1/2 | Active, Recruiting |
NCT04142619 | SLAMF7 | UCARTCS1 | Cellectis S.A | 1 | Active, Recruiting |
NCT03464916 | CD38 | CAR2 Anti-CD38 A2 | Sorrento Therapeutics, Inc. | 1 | Completed |
NCT03767751 | CD38 | NA | Chinese PLA General Hospital | 1/2 | Unknown |
NCT02135406 | CD19 | CTL019/tisagenlecleucel | University of Pennsylvania | 1 | Completed |
NCT03672318 | CD138 | ATLCAR.CD138 | UNC Lineberger Comprehensive Cancer Center | 1 | Active, Recruiting |
NCT01886976 | CD138 | CART-138 | Chinese PLA General Hospital | 1/2 | Unknown |
NCT04182581 | BCMA/CD19 | BCMA/CD19 Dual-Target | Xijing Hospital | Early Phase1 | Unknown |
NCT03706547 | CD19 | NA | Peng Liu Peng Liu, Shanghai Zhongshan Hospital | 1 | Unknown |
NCT04714827 | CD19 | CD19-CD22 | Shanxi Province Cancer Hospital | 1/2 | Recruiting |
NCT04541368 | SLAMF7 | CS1 | Zhejiang University He Huang, Zhejiang University | Early Phase 1 | Not Yet Recruiting |
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Mishra, A.K.; Gupta, A.; Dagar, G.; Das, D.; Chakraborty, A.; Haque, S.; Prasad, C.P.; Singh, A.; Bhat, A.A.; Macha, M.A.; et al. CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond. Vaccines 2023, 11, 1721. https://doi.org/10.3390/vaccines11111721
Mishra AK, Gupta A, Dagar G, Das D, Chakraborty A, Haque S, Prasad CP, Singh A, Bhat AA, Macha MA, et al. CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond. Vaccines. 2023; 11(11):1721. https://doi.org/10.3390/vaccines11111721
Chicago/Turabian StyleMishra, Abhinava K., Ashna Gupta, Gunjan Dagar, Dayasagar Das, Abhijit Chakraborty, Shabirul Haque, Chandra Prakash Prasad, Archana Singh, Ajaz A. Bhat, Muzafar A. Macha, and et al. 2023. "CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond" Vaccines 11, no. 11: 1721. https://doi.org/10.3390/vaccines11111721