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@ARTICLE{Rausch:284610,
author = {J. Rausch$^*$ and E. Ullrich$^*$ and M. W. M. Kühn$^*$},
title = {{E}pigenetic targeting to enhance acute myeloid
leukemia-directed immunotherapy.},
journal = {Frontiers in immunology},
volume = {14},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2023-02030},
pages = {1269012},
year = {2023},
abstract = {AML is a malignant disease of hematopoietic progenitor
cells with unsatisfactory treatment outcome, especially in
patients that are ineligible for intensive chemotherapy.
Immunotherapy, comprising checkpoint inhibition, T-cell
engaging antibody constructs, and cellular therapies, has
dramatically improved the outcome of patients with solid
tumors and lymphatic neoplasms. In AML, these approaches
have been far less successful. Discussed reasons are the
relatively low mutational burden of AML blasts and the
difficulty in defining AML-specific antigens not expressed
on hematopoietic progenitor cells. On the other hand,
epigenetic dysregulation is an essential driver of
leukemogenesis, and non-selective hypomethylating agents
(HMAs) are the current backbone of non-intensive treatment.
The first clinical trials that evaluated whether HMAs may
improve immune checkpoint inhibitors' efficacy showed modest
efficacy except for the anti-CD47 antibody that was
substantially more efficient against AML when combined with
azacitidine. Combining bispecific antibodies or cellular
treatments with HMAs is subject to ongoing clinical
investigation, and efficacy data are awaited shortly. More
selective second-generation inhibitors targeting specific
chromatin regulators have demonstrated promising preclinical
activity against AML and are currently evaluated in clinical
trials. These drugs that commonly cause leukemia cell
differentiation potentially sensitize AML to immune-based
treatments by co-regulating immune checkpoints, providing a
pro-inflammatory environment, and inducing (neo)-antigen
expression. Combining selective targeted epigenetic drugs
with (cellular) immunotherapy is, therefore, a promising
approach to avoid unintended effects and augment efficacy.
Future studies will provide detailed information on how
these compounds influence specific immune functions that may
enable translation into clinical assessment.},
subtyp = {Review Article},
keywords = {acute myeloid leukemia (Other) / cellular therapy (Other) /
checkpoint inhibition (Other) / chromatin modifiers (Other)
/ combination therapy (Other) / epigenetics (Other) /
hypomethylating agents (Other) / immunotherapy (Other)},
cin = {FM01},
ddc = {610},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37809078},
pmc = {pmc:PMC10556528},
doi = {10.3389/fimmu.2023.1269012},
url = {https://inrepo02.dkfz.de/record/284610},
}