Cell-based and antibody-mediated immunotherapies directed against leukemic stem cells in acute myeloid leukemia: Perspectives and open issues.
CAR-T and CAR-NK cell-therapy
bi-specific antibodies
immune-checkpoints
leukemic stem cells
precision medicine
stem cell resistance
Journal
Stem cells translational medicine
ISSN: 2157-6580
Titre abrégé: Stem Cells Transl Med
Pays: England
ID NLM: 101578022
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
08
04
2020
revised:
18
05
2020
accepted:
04
06
2020
pubmed:
14
7
2020
medline:
3
9
2021
entrez:
14
7
2020
Statut:
ppublish
Résumé
Despite new insights in molecular features of leukemic cells and the availability of novel treatment approaches and drugs, acute myeloid leukemia (AML) remains a major clinical challenge. In fact, many patients with AML relapse after standard therapy and eventually die from progressive disease. The basic concept of leukemic stem cells (LSC) has been coined with the goal to decipher clonal architectures in various leukemia-models and to develop curative drug therapies by eliminating LSC. Indeed, during the past few years, various immunotherapies have been tested in AML, and several of these therapies follow the strategy to eliminate relevant leukemic subclones by introducing LSC-targeting antibodies or LSC-targeting immune cells. These therapies include, among others, new generations of LSC-eliminating antibody-constructs, checkpoint-targeting antibodies, bi-specific antibodies, and CAR-T or CAR-NK cell-based strategies. However, responses are often limited and/or transient which may be due to LSC resistance. Indeed, AML LSC exhibit multiple forms of resistance against various drugs and immunotherapies. An additional problems are treatment-induced myelotoxicity and other side effects. The current article provides a short overview of immunological targets expressed on LSC in AML. Moreover, cell-based therapies and immunotherapies tested in AML are discussed. Finally, the article provides an overview about LSC resistance and strategies to overcome resistance.
Identifiants
pubmed: 32657052
doi: 10.1002/sctm.20-0147
pmc: PMC7581453
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1331-1343Informations de copyright
© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.
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