The long road to the first FDA-approved gene therapy: chimeric antigen receptor T cells targeting CD19.
Adult
Antibodies, Bispecific
Antigens, CD19
/ immunology
Cell Count
Cell- and Tissue-Based Therapy
/ methods
Genetic Engineering
Genetic Therapy
/ methods
Humans
Immunotherapy
/ methods
Immunotherapy, Adoptive
Lymphoma, B-Cell
/ immunology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ immunology
Receptors, Antigen, T-Cell
/ therapeutic use
Receptors, Chimeric Antigen
/ genetics
T-Lymphocytes
/ immunology
United States
United States Food and Drug Administration
CART
CART19
CTL019, tisagenlecleucel
axicabtagene ciloleucel
chimeric antigen receptor T cells
Journal
Cytotherapy
ISSN: 1477-2566
Titre abrégé: Cytotherapy
Pays: England
ID NLM: 100895309
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
15
10
2019
revised:
27
11
2019
accepted:
01
12
2019
pubmed:
6
2
2020
medline:
23
7
2020
entrez:
5
2
2020
Statut:
ppublish
Résumé
Thirty years after initial publications of the concept of a chimeric antigen receptor (CAR), the U.S. Food and Drug Administration (FDA) approved the first anti-CD19 CAR T-cell therapy. Unlike other immunotherapies, such as immune checkpoint inhibitors and bispecific antibodies, CAR T cells are unique as they are "living drugs," that is, gene-edited killer cells that can recognize and kill cancer. During these 30 years of development, the CAR construct, T-cell manufacturing process, and clinical patient management have gone through rounds of failures and successes that drove continuous improvement. Tisagenlecleucel was the first gene therapy to receive approval from the FDA for any indication. The initial approval was for relapsed or refractory (r/r) pediatric and young-adult B-cell acute lymphoblastic leukemia in August 2017 and in May 2018 for adult r/r diffuse large B-cell lymphoma. Here we review the preclinical and clinical development of what began as CART19 at the University of Pennsylvania and later developed into tisagenlecleucel.
Identifiants
pubmed: 32014447
pii: S1465-3249(19)30918-1
doi: 10.1016/j.jcyt.2019.12.004
pmc: PMC7036015
mid: NIHMS1546118
pii:
doi:
Substances chimiques
Antibodies, Bispecific
0
Antigens, CD19
0
Receptors, Antigen, T-Cell
0
Receptors, Chimeric Antigen
0
tisagenlecleucel
Q6C9WHR03O
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
57-69Subventions
Organisme : NCI NIH HHS
ID : K99 CA212302
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA214278
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA212302
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA166961
Pays : United States
Informations de copyright
Copyright © 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.
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