Chimeric Antigen Receptor T-Cell Therapy and Hematopoiesis
Abstract
:1. Introduction
2. Incidence and Characteristics of CAR T-Associated Cytopenias
3. Factors Associated with Post-CAR T Cytopenias
4. Pre-Treatment Cytopenias and Reduced CAR T Efficacy
5. Implications of Age-Associated Inflammation on Bone Marrow and CAR T Outcomes
6. Approaches to Mitigating and Managing Cytopenias
6.1. Paracrine Factor Modulation
6.2. Allogeneic Hematopoietic Cell Transplant following CAR T-Cell Therapy
6.3. Autologous Hematopoietic Stem Cell Boost Post CAR T
6.4. Alternative Conditioning Regimens
7. Alternative Approaches to Optimizing CAR T-Cell Therapy Regimens
7.1. Repeat Dosing
7.2. Optimizing the CAR T-Cell Infusion Product Composition
7.3. Optimizing the CAR Construct
8. CAR T and Immune Cell Interaction
9. CAR T and Clonal Hematopoiesis
10. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Reference | Sample Size | Disease | Study | CAR Construct | Incidence of Prolonged Persistent Cytopenia |
---|---|---|---|---|---|
Locke et al. [4] | 119 | DLBCL, PMBCL, t FL | ZUMA-1 (phase I/II) | Anti-CD19, CD28 co-stimulatory domain (retroviral) | 7%, 11%, (>3 mo) |
Schuster SJ et al. [8] | 167 | DLBCL | JULIET (phase II) | Anti-CD19, 4-1BB co-stimulatory domain (lentiviral) | 32%, (>1 mo) |
Wang et al. [40] | 74 | MCL | KTE-X19 (phase II) | Anti-CD19, CD28 co-stimulatory domain (retroviral) | 16%, 16%, (>3 mo) |
Maude et al. [48] | 75 | B-ALL (children and young adults) | ELIANA (phase I/II) | Anti-CD19, 4-1BB co-stimulatory domain (lentiviral) | 12%, 53%, (>1 mo) |
Lee et al. [65] | 53 | B-ALL (children) | NCT01044069 (phase I) | Anti-CD19, 4-1BB co-stimulatory domain (lentiviral) | 33%, (>14 days) |
Reference | Study | CAR Construct | Anemia | Thrombocytopenia | Neutropenia | CRS | ICANS | Infections |
---|---|---|---|---|---|---|---|---|
Locke et al. [4] | ZUMA-1 (phase I/II) | Anti-CD19, CD28 co-stimulatory domain (retroviral) | 43% | 38% | 78% | 13% | 28% | 8% |
Schuster SJ et al. [8] | JULIET (phase II) | Anti-CD19, 4-1BB co-stimulatory domain (lentiviral) | 39% | 28% | 33% | 22% | 12% | 20% |
Wang et al. [40] | KTE-X19 (phase II) | Anti-CD19, CD28 co-stimulatory domain (retroviral) | 50% | 51% | 85% | 15% | 31% | 32% |
Maude et al. [48] | ELIANA (phase I/II) | Anti-CD19, 4-1BB co-stimulatory domain (lentiviral) | Not reported | 41% | 35% | 46% | 13% | 24% |
Lee et al. [65] | NCT01044069 (phase I) | Anti-CD19, 4-1BB co-stimulatory domain (lentiviral) | 68% | 53% | >50% | 40% | 0% | Not reported |
Shah B.D. et al. [67] | ZUMA-3 (phase II) | Anti-CD19, CD28 co-stimulatory domain (retroviral) | 49% | 30% | 27% | 24% | 25% | 25% |
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Reinhardt, B.; Lee, P.; Sasine, J.P. Chimeric Antigen Receptor T-Cell Therapy and Hematopoiesis. Cells 2023, 12, 531. https://doi.org/10.3390/cells12040531
Reinhardt B, Lee P, Sasine JP. Chimeric Antigen Receptor T-Cell Therapy and Hematopoiesis. Cells. 2023; 12(4):531. https://doi.org/10.3390/cells12040531
Chicago/Turabian StyleReinhardt, Bryanna, Patrick Lee, and Joshua P. Sasine. 2023. "Chimeric Antigen Receptor T-Cell Therapy and Hematopoiesis" Cells 12, no. 4: 531. https://doi.org/10.3390/cells12040531
APA StyleReinhardt, B., Lee, P., & Sasine, J. P. (2023). Chimeric Antigen Receptor T-Cell Therapy and Hematopoiesis. Cells, 12(4), 531. https://doi.org/10.3390/cells12040531