Chimeric Antigen Receptor T-Cell Therapy and Hematopoiesis.

Autor: Reinhardt B; School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA., Lee P; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Sasine JP; Department of Medicine, Division of Hematology and Cellular Therapy, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 Feb 07; Vol. 12 (4). Date of Electronic Publication: 2023 Feb 07.
DOI: 10.3390/cells12040531
Abstrakt: Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome (MAS), and prolonged cytopenias-a reduction in the number of mature blood cells of one or more lineage. Although we understand some drivers of these toxicities, their mechanisms remain under investigation. Since the CAR T regimen is a complex, multi-step process with frequent adverse events, ways to improve the benefit-to-risk ratio are needed. In this review, we discuss a variety of potential solutions being investigated to address the limitations of CAR T. First, we discuss the incidence and characteristics of CAR T-related cytopenias and their association with reduced CAR T-cell efficacy. We review approaches to managing or mitigating cytopenias during the CAR T regimen-including the use of growth factors, allogeneic rescue, autologous hematopoietic stem cell infusion, and alternative conditioning regimens. Finally, we introduce novel methods to improve CAR T-cell-infusion products and the implications of CAR T and clonal hematopoiesis.
Databáze: MEDLINE
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