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Chimeric antigen receptor T-cell therapy in childhood acute myeloid leukemia: how far are we from a clinical application?
- Source :
-
Haematologica [Haematologica] 2024 Jun 01; Vol. 109 (6), pp. 1656-1667. Date of Electronic Publication: 2024 Jun 01. - Publication Year :
- 2024
-
Abstract
- Recurrent and/or refractory (R/R) pediatric acute myeloid leukemia (AML) remains a recalcitrant disease with poor outcomes. Cell therapy with genetically modified immune effector cells holds the promise to improve outcomes for R/R AML since it relies on cytotoxic mechanisms that are distinct from chemotherapeutic agents. While T cells expressing chimeric antigen receptors (CAR T cells) showed significant anti-AML activity in preclinical models, early phase clinical studies have demonstrated limited activity, irrespective of the targeted AML antigen. Lack of efficacy is most likely multifactorial, including: (i) a limited array of AML-specific targets and target antigen heterogeneity; (ii) the aggressive nature of R/R AML and heavy pretreatment of patients; (iii) T-cell product manufacturing, and (iv) limited expansion and persistence of the CAR T cells, which is in part driven by the immunosuppressive AML microenvironment. Here we review the results of early phase clinical studies with AML-specific CAR T cells, and avenues investigators are exploring to improve their effector function.
- Subjects :
- Humans
Child
Clinical Trials as Topic
T-Lymphocytes immunology
T-Lymphocytes metabolism
Treatment Outcome
Receptors, Antigen, T-Cell immunology
Receptors, Antigen, T-Cell genetics
Tumor Microenvironment immunology
Animals
Leukemia, Myeloid, Acute therapy
Leukemia, Myeloid, Acute immunology
Receptors, Chimeric Antigen immunology
Immunotherapy, Adoptive methods
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 109
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 38832421
- Full Text :
- https://doi.org/10.3324/haematol.2023.283817