Pre-clinical assessment of chimeric antigen receptor t cell therapy targeting CD19+ B cell malignancy.
CD19
Chimeric antigen receptor (CAR)
UWC19
immunodeficient mice
safety evaluation
tumorigenicity
Journal
Annals of translational medicine
ISSN: 2305-5839
Titre abrégé: Ann Transl Med
Pays: China
ID NLM: 101617978
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
entrez:
23
6
2020
pubmed:
23
6
2020
medline:
23
6
2020
Statut:
ppublish
Résumé
Autologous chimeric antigen receptor (CAR) T cell therapy is a promising therapeutic strategy for treating hematologic malignancies. A spectrum of serious complications caused by CAR-T cells has caught great attention. We developed a novel CAR against CD19 namely UWC19, consisting anti-CD19 single-chain variable fragment (scFv) hinged with 4-1BB and CD3z signaling domains. In this study, preclinical assessments of UWC19 were conducted to evaluate the safety and efficacy To evaluate the binding activity of UWC19 cells to CD19, we measured the saturation degree of CAR with human CD19 molecules using flow cytometry We showed that UWC19 CAR T cells exerted highly specific binding affinity and cytotoxicity against CD19+ cells UWC19 treatment effectively eliminated CD19 positive tumor cells with favorable toxicity profile. The findings suggest encouraging clinical prospects for its use in patients with CD19 positive B cell malignancies. Our study presented an alternative evaluation strategy for CAR-T cell products.
Sections du résumé
BACKGROUND
BACKGROUND
Autologous chimeric antigen receptor (CAR) T cell therapy is a promising therapeutic strategy for treating hematologic malignancies. A spectrum of serious complications caused by CAR-T cells has caught great attention. We developed a novel CAR against CD19 namely UWC19, consisting anti-CD19 single-chain variable fragment (scFv) hinged with 4-1BB and CD3z signaling domains. In this study, preclinical assessments of UWC19 were conducted to evaluate the safety and efficacy
METHODS
METHODS
To evaluate the binding activity of UWC19 cells to CD19, we measured the saturation degree of CAR with human CD19 molecules using flow cytometry
RESULTS
RESULTS
We showed that UWC19 CAR T cells exerted highly specific binding affinity and cytotoxicity against CD19+ cells
CONCLUSIONS
CONCLUSIONS
UWC19 treatment effectively eliminated CD19 positive tumor cells with favorable toxicity profile. The findings suggest encouraging clinical prospects for its use in patients with CD19 positive B cell malignancies. Our study presented an alternative evaluation strategy for CAR-T cell products.
Identifiants
pubmed: 32566611
doi: 10.21037/atm.2020.02.148
pii: atm-08-09-584
pmc: PMC7290534
doi:
Types de publication
Journal Article
Langues
eng
Pagination
584Informations de copyright
2020 Annals of Translational Medicine. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.02.148). The authors have no conflicts of interest to declare.
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