Evaluation of switch-mediated costimulation in trans on universal CAR-T cells (UniCAR) targeting CD123-positive AML.
4-1BB
CD123
Chimeric antigen receptor (CAR)
acute myeloid leukemia (AML)
costimulation in trans
switchable CAR platform
Journal
Oncoimmunology
ISSN: 2162-402X
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
22
7
2021
pubmed:
23
7
2021
medline:
3
8
2021
Statut:
epublish
Résumé
Chimeric antigen receptor T cells (CAR-T) targeting CD19 have achieved significant success in patients with B cell malignancies. To date, implementation of CAR-T in other indications remains challenging due to the lack of truly tumor-specific antigens as well as control of CAR-T activity in patients. CD123 is highly expressed in acute myeloid leukemia (AML) blasts including leukemia-initiating cells making it an attractive immunotherapeutic target. However, CD123 expression in normal hematopoietic progenitor cells and endothelia bears the risk of severe toxicities and may limit CAR-T applications lacking fine-tuned control mechanisms. Therefore, we recently developed a rapidly switchable universal CAR-T platform (UniCAR), in which CAR-T activity depends on the presence of a soluble adapter called targeting module (TM), and confirmed clinical proof-of-concept for targeting CD123 in AML with improved safety. As costimulation via 4-1BB ligand (4-1BBL) can enhance CAR-T expansion, persistence, and effector functions, a novel CD123-specific TM variant (TM123-4-1BBL) comprising trimeric single-chain 4-1BBL was developed for transient costimulation of UniCAR-T cells (UniCAR-T) at the leukemic site
Identifiants
pubmed: 34290907
doi: 10.1080/2162402X.2021.1945804
pii: 1945804
pmc: PMC8274446
doi:
Substances chimiques
Antigens, Neoplasm
0
Interleukin-3 Receptor alpha Subunit
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1945804Informations de copyright
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
Déclaration de conflit d'intérêts
Conflict-of-interest-disclosure: GE and AE are shareholders of GEMoaB GmbH and CPT Cellex Patient Treatment GmbH. JEM, SL, JD, JS, GJJ, MC, and AE are employees at GEMoaB GmbH and/or its subsidiary company CPT Cellex Patient Treatment GmbH.
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