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@ARTICLE{Fetsch:277752,
      author       = {V. Fetsch and R. Zeiser$^*$},
      title        = {{C}himeric antigen receptor {T} cells for acute myeloid
                      leukemia.},
      journal      = {European journal of haematology},
      volume       = {112},
      number       = {1},
      issn         = {0902-4441},
      address      = {Oxford},
      publisher    = {Wiley-Blackwell},
      reportid     = {DKFZ-2023-01469},
      pages        = {28-35},
      year         = {2024},
      note         = {2024 Jan;112(1):28-35},
      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.},
      subtyp        = {Review Article},
      keywords     = {CAR T cells (Other) / acute myeloid leukemia (Other) /
                      immune escape (Other) / multitargeted CAR T cells (Other) /
                      myelotoxicity (Other)},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37455578},
      doi          = {10.1111/ejh.14047},
      url          = {https://inrepo02.dkfz.de/record/277752},
}