Controlled release of enhanced cross-hybrid IgGA Fc PD-L1 inhibitors using oncolytic adenoviruses.
Fc engineering
IgA
IgG
PD-L1 therapy
oncolytic adenoviruses
Journal
Molecular therapy oncolytics
ISSN: 2372-7705
Titre abrégé: Mol Ther Oncolytics
Pays: United States
ID NLM: 101666776
Informations de publication
Date de publication:
16 Mar 2023
16 Mar 2023
Historique:
received:
31
08
2022
accepted:
31
01
2023
entrez:
13
3
2023
pubmed:
14
3
2023
medline:
14
3
2023
Statut:
epublish
Résumé
Immune checkpoint inhibitors have clinical success in prolonging the life of many cancer patients. However, only a minority of patients benefit from such therapy, calling for further improvements. Currently, most PD-L1 checkpoint inhibitors in the clinic do not elicit Fc effector mechanisms that would substantially increase their efficacy. To gain potency and circumvent off-target effects, we previously designed an oncolytic adenovirus (Ad-Cab) expressing an Fc fusion peptide against PD-L1 on a cross-hybrid immunoglobulin GA (IgGA) Fc. Ad-Cab elicited antibody effector mechanisms of IgG1 and IgA, which led to higher tumor killing compared with each isotype alone and with clinically approved PD-L1 checkpoint inhibitors. In this study, we further improved the therapy to increase the IgG1 Fc effector mechanisms of the IgGA Fc fusion peptide (Ad-Cab FT) by adding four somatic mutations that increase natural killer (NK) cell activation. Ad-Cab FT was shown to work better at lower concentrations compared with Ad-Cab
Identifiants
pubmed: 36911070
doi: 10.1016/j.omto.2023.01.006
pii: S2372-7705(23)00008-6
pmc: PMC9995465
doi:
Types de publication
Journal Article
Langues
eng
Pagination
264-276Informations de copyright
© 2023.
Déclaration de conflit d'intérêts
V.C. is a co-founder and shareholder of Valo Therapeutics LTD (not related to this study).
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