TY  - JOUR
AU  - Fetsch, Viktor
AU  - Zeiser, Robert
TI  - Chimeric antigen receptor T cells for acute myeloid leukemia.
JO  - European journal of haematology
VL  - 112
IS  - 1
SN  - 0902-4441
CY  - Oxford
PB  - Wiley-Blackwell
M1  - DKFZ-2023-01469
SP  - 28-35
PY  - 2024
N1  - 2024 Jan;112(1):28-35
AB  - The use of T cells expressing chimeric antigen receptors (CARs) that can target and eliminate cancer cells has revolutionized the treatment of B-cell malignancies. In contrast, CAR T cells have not yet become a routine treatment for myeloid malignancies such as acute myeloid leukemia (AML) or myeloproliferative neoplasms (MPNs). For these disease entities, allogeneic hematopoietic cell transplantation (allo-HCT) relying on polyclonal allo-reactive T cells is still the major cellular immunotherapy used in clinical routine. Here, we discuss major hurdles of CAR T-cell therapy for myeloid malignancies and novel approaches to enhance their efficacy and reduce toxicity. Heterogeneity of the malignant myeloid clone, CAR T-cell induced toxicity against normal hematopoietic cells, lack of long-term CAR T-cell persistence, and loss or downregulation of targetable antigens on myeloid cells are obstacles for successful CAR T cells therapy against AML and MPNs. Strategies to overcome these hurdles include pharmacological interventions, for example, demethylating therapy to increase target antigen expression, multi-targeted CAR T cells, and gene-therapy based approaches that delete the CAR target antigen in the hematopoietic cells of the recipient to protect them from CAR-induced myelotoxicity. Most of these approaches are still in preclinical testing but may reach the clinic in the coming years. In summary, we report on barriers to CAR T-cell use against AML and novel therapeutic strategies to overcome these challenges, with the goal of clinical treatment of myeloid malignancies with CAR T cells.
KW  - CAR T cells (Other)
KW  - acute myeloid leukemia (Other)
KW  - immune escape (Other)
KW  - multitargeted CAR T cells (Other)
KW  - myelotoxicity (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37455578
DO  - DOI:10.1111/ejh.14047
UR  - https://inrepo02.dkfz.de/record/277752
ER  -