Current Limitations and Perspectives of Chimeric Antigen Receptor-T-Cells in Acute Myeloid Leukemia.
Marius MaucherMicha SrourSophia DanhofHermann EinseleMichael HudecekIbrahim Yakoub AghaPublished in: Cancers (2021)
Adoptive transfer of gene-engineered chimeric antigen receptor (CAR)-T-cells has emerged as a powerful immunotherapy for combating hematologic cancers. Several target antigens that are prevalently expressed on AML cells have undergone evaluation in preclinical CAR-T-cell testing. Attributes of an 'ideal' target antigen for CAR-T-cell therapy in AML include high-level expression on leukemic blasts and leukemic stem cells (LSCs), and absence on healthy tissues, normal hematopoietic stem and progenitor cells (HSPCs). In contrast to other blood cancer types, where CAR-T therapies are being similarly studied, only a rather small number of AML patients has received CAR-T-cell treatment in clinical trials, resulting in limited clinical experience for this therapeutic approach in AML. For curative AML treatment, abrogation of bulk blasts and LSCs is mandatory with the need for hematopoietic recovery after CAR-T administration. Herein, we provide a critical review of the current pipeline of candidate target antigens and corresponding CAR-T-cell products in AML, assess challenges for clinical translation and implementation in routine clinical practice, as well as perspectives for overcoming them.
Keyphrases
- acute lymphoblastic leukemia
- mesenchymal stem cells
- cell therapy
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- bone marrow
- stem cells
- clinical practice
- clinical trial
- end stage renal disease
- induced apoptosis
- magnetic resonance
- newly diagnosed
- healthcare
- gene expression
- dendritic cells
- magnetic resonance imaging
- ejection fraction
- chronic kidney disease
- prognostic factors
- poor prognosis
- randomized controlled trial
- immune response
- papillary thyroid
- rectal cancer
- signaling pathway
- oxidative stress
- replacement therapy
- cell proliferation
- long non coding rna
- childhood cancer