Design and Synthesis of A PD-1 Binding Peptide and Evaluation of Its Anti-Tumor Activity.
FITC-YT-16 peptide
PD-1
PD-L1
T cells
cytokines
tumor
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
29 Jan 2019
29 Jan 2019
Historique:
received:
11
01
2019
revised:
26
01
2019
accepted:
27
01
2019
entrez:
1
2
2019
pubmed:
1
2
2019
medline:
14
5
2019
Statut:
epublish
Résumé
Immune-checkpoint blockades, suchas PD-1 monoclonal antibodies, have shown new promising avenues to treat cancers. Failure responsesof many cancer patients to these agents have led to a massive need for alternative strategies to optimize tumor immunotherapy. Currently, new therapeutic developments involve peptide blocking strategies, as they have high stability and low immunogenicity. Here, we have designed and synthesized a new peptide FITC-YT-16 to target PD-1. We have studied FITC-YT-16 by various experiments, including Molecular Operating Environment MOE modeling, purification testing by HPLC and LC mass, peptide/PD-1 conjugation and affinity by microscale thermophoresis (MST), and T cell immune-fluorescence imaging by fluorescence microscopy and flow cytometry. The peptide was tested for its ability to enhanceT cell activity against tumor cell lines, including TE-13, A549, and MDA-MB-231. Lastly, we assessed T cell cytotoxicity under peptide treatment. YT-16⁻PD-1 interaction showed a high binding affinity as a low energy complex that was confirmed by MOE. Furthermore, the peptide purity and molecular weights were 90.96% and 2344.66, respectively. MST revealed that FITC-YT-16 interacted with PD-1 at a K
Identifiants
pubmed: 30699956
pii: ijms20030572
doi: 10.3390/ijms20030572
pmc: PMC6386944
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents
0
Interleukin-2
0
Programmed Cell Death 1 Receptor
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : the Project Program of State Key Laboratory of Natural Medicines
ID : no. SKLNMBZ201403
Organisme : the National Science and Technology Major Projects of New Drugs
ID : 2018ZX09201001004001, 2018ZX09301039002, 2018ZX09301053001
Organisme : the Priority Academic Program Development of Jiangsu Higher Education Institutions
ID : PAPD
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