Journal Article (Review Article)

DKFZ-2023-01469

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Chimeric antigen receptor T cells for acute myeloid leukemia.

Fetsch, V. ; Zeiser, R.DKFZ*

2024
Wiley-Blackwell Oxford

This record in other databases:  

Please use a persistent id in citations: doi:10.1111/ejh.14047

Abstract: 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.

Keyword(s): CAR T cells ; acute myeloid leukemia ; immune escape ; multitargeted CAR T cells ; myelotoxicity

Note: 2024 Jan;112(1):28-35

---

Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---