1. Chimeric antigen receptor T-cell therapy in childhood acute myeloid leukemia: how far are we from a clinical application?
- Author
-
Naik S, Velasquez MP, and Gottschalk S
- 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
- 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.
- Published
- 2024
- Full Text
- View/download PDF