Combining CRISPR-Cas9 and TCR exchange to generate a safe and efficient cord blood-derived T cell product for pediatric relapsed AML.
CD8-Positive T-Lymphocytes
Cell Engineering
Hematologic Neoplasms
Pediatrics
T cell Receptor - TCR
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
05 Apr 2024
05 Apr 2024
Historique:
accepted:
18
03
2024
medline:
6
4
2024
pubmed:
6
4
2024
entrez:
5
4
2024
Statut:
epublish
Résumé
Hematopoietic cell transplantation (HCT) is an effective treatment for pediatric patients with high-risk, refractory, or relapsed acute myeloid leukemia (AML). However, a large proportion of transplanted patients eventually die due to relapse. To improve overall survival, we propose a combined strategy based on cord blood (CB)-HCT with the application of AML-specific T cell receptor (TCR)-engineered T cell therapy derived from the same CB graft. We produced CB-CD8 The gene editing and transduction procedures achieved high efficiency, with up to 95% of cells lacking eTCR and over 70% of T cells expressing rWT1-TCR. WT1-TCR-engineered T cells lacking the expression of their eTCR (eTCR In summary, we show the feasibility of developing a potent CB-derived CD8
Sections du résumé
BACKGROUND
BACKGROUND
Hematopoietic cell transplantation (HCT) is an effective treatment for pediatric patients with high-risk, refractory, or relapsed acute myeloid leukemia (AML). However, a large proportion of transplanted patients eventually die due to relapse. To improve overall survival, we propose a combined strategy based on cord blood (CB)-HCT with the application of AML-specific T cell receptor (TCR)-engineered T cell therapy derived from the same CB graft.
METHODS
METHODS
We produced CB-CD8
RESULTS
RESULTS
The gene editing and transduction procedures achieved high efficiency, with up to 95% of cells lacking eTCR and over 70% of T cells expressing rWT1-TCR. WT1-TCR-engineered T cells lacking the expression of their eTCR (eTCR
CONCLUSIONS
CONCLUSIONS
In summary, we show the feasibility of developing a potent CB-derived CD8
Identifiants
pubmed: 38580329
pii: jitc-2023-008174
doi: 10.1136/jitc-2023-008174
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: JK reports grants from Gadeta, Novartis, and Miltenyi Biotec and is the inventor of patents dealing with γδT cell-related aspects, as well as the cofounder and shareholder of Gadeta. ZS is an inventor of patents dealing with γδT cell-related aspects.