Engineering of an Avidity-Optimized CD19-Specific Parallel Chimeric Antigen Receptor That Delivers Dual CD28 and 4-1BB Co-Stimulation.
4-1BB
CD19
CD28
avidity
chimeric antigen receptor
co-stimulation
parallel CAR
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
15
12
2021
accepted:
20
01
2022
entrez:
28
2
2022
pubmed:
1
3
2022
medline:
9
4
2022
Statut:
epublish
Résumé
Co-stimulation is critical to the function of chimeric antigen receptor (CAR) T-cells. Previously, we demonstrated that dual co-stimulation can be effectively harnessed by a parallel (p)CAR architecture in which a CD28-containing second generation CAR is co-expressed with a 4-1BB containing chimeric co-stimulatory receptor (CCR). When compared to linear CARs, pCAR-engineered T-cells elicit superior anti-tumor activity in a range of pre-clinical models. Since CD19 is the best validated clinical target for cellular immunotherapy, we evaluated a panel of CD19-specific CAR and pCAR T-cells in this study. First, we generated a panel of single chain antibody fragments (scFvs) by alanine scanning mutagenesis of the CD19-specific FMC63 scFv (V
Identifiants
pubmed: 35222427
doi: 10.3389/fimmu.2022.836549
pmc: PMC8863855
doi:
Substances chimiques
Antigens, CD19
0
CD28 Antigens
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
836549Subventions
Organisme : Medical Research Council
ID : MR/R001936/1
Pays : United Kingdom
Organisme : Department of Health
ID : IS-BRC-1215-20006
Pays : United Kingdom
Informations de copyright
Copyright © 2022 Halim, Das, Larcombe-Young, Ajina, Candelli, Benjamin, Dillon, Davies and Maher.
Déclaration de conflit d'intérêts
JM is CSO, scientific founder and shareholder of Leucid Bio, is a member of the scientific advisory board of Arovella Pharmaceutics Ltd and has undertaken consultancy work for Bristol-Meyers-Squibb, Juno, Celgene, Ellipses Pharma and Biotest. LH undertook a PhD studentship funded by Leucid Bio. DD and DL-Y have acted as consultants for Leucid Bio and DD has been employed by Leucid Bio following completion of this work. JM and LH are co-inventors on patent filings in relation to pCAR technology. KD and AC are employees of Lumicks. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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