Formatting and gene-based delivery of a human PD-L1 single domain antibody for immune checkpoint blockade.
gene therapy
nanobody
programmed death-ligand 1
single domain antibody
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
10 Sep 2021
10 Sep 2021
Historique:
received:
24
11
2020
accepted:
27
05
2021
entrez:
6
9
2021
pubmed:
7
9
2021
medline:
7
9
2021
Statut:
epublish
Résumé
Monoclonal antibodies that target the inhibitory immune checkpoint axis consisting of programmed cell death protein 1 (PD-1) and its ligand, PD-L1, have changed the immune-oncology field. We identified K2, an anti-human PD-L1 single-domain antibody fragment, that can enhance T cell activation and tumor cell killing. In this study, the potential of different K2 formats as immune checkpoint blocking medicines was evaluated using a gene-based delivery approach. We showed that 2K2 and 3K2, a bivalent and trivalent K2 format generated using a 12 GS (glycine-serine) linker, were 313- and 135-fold more potent in enhancing T cell receptor (TCR) signaling in PD-1
Identifiants
pubmed: 34485603
doi: 10.1016/j.omtm.2021.05.017
pii: S2329-0501(21)00101-7
pmc: PMC8397838
doi:
Types de publication
Journal Article
Langues
eng
Pagination
172-182Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
K. Broos, Q.L., G.R., N.D., M.K., and K. Breckpot have patents on the use of K2 for imaging and therapy purposes (WO2019166622A1; Human pd-l1-binding immunoglobulins). M.K. received research funding from Precirix. M.K., G.R., and N.D. hold ownership interest in Abscint NV/SA. G.R. and N.D. are consultants for and hold ownership interest in Precirix. N.D. has received funding for pre-clinical research from Boehringer-Ingelheim, Complix, ConfoTherapeutics, Roche, 121BIO, Agenus, and Telix Pharma. The remaining authors declare no competing interests.
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