FGF2-Derived PeptibodyF2-MMAE Conjugate for Targeted Delivery of Cytotoxic Drugs into Cancer Cells Overexpressing FGFR1

Fibroblast growth factor receptors (FGFRs) are emerging targets for directed cancer therapy. Presented here is a new FGFR1-targeting conjugate, the peptibodyF2, which employs peptibody, a fusion of peptide and the Fc fragment of human IgG as a selective targeting agent and drug carrier. Short peptid...

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Bibliographic Details
Published in:Cancers 2020-10, Vol.12 (10), p.2992
Main Authors: Jendryczko, Karolina, Chudzian, Julia, Skinder, Natalia, Opaliński, Łukasz, Rzeszótko, Jakub, Wiedlocha, Antoni, Otlewski, Jacek, Szlachcic, Anna
Format: Article
Language:English
Subjects:
Binding sites
Cancer therapies
Cancer treatment
Cell division
Cytotoxicity
Drug delivery
Drug targeting
Fibroblast growth factor 2
Fibroblast growth factor receptor 1
Fibroblast growth factor receptors
Fibroblasts
Growth factor receptors
Growth factors
Immunoglobulin G
Kinases
Ligands
Lung carcinoma
Methods
Monoclonal antibodies
Peptides
Pharmacokinetics
Phosphorylation
Physiological aspects
Receptor mechanisms
Signal transduction
Tumors
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Summary:Fibroblast growth factor receptors (FGFRs) are emerging targets for directed cancer therapy. Presented here is a new FGFR1-targeting conjugate, the peptibodyF2, which employs peptibody, a fusion of peptide and the Fc fragment of human IgG as a selective targeting agent and drug carrier. Short peptide based on FGF2 sequence was used to construct a FGFR1-targeting peptibody. We have shown that this peptide ensures specific delivery of peptibodyF2 into FGFR1-expressing cells. In order to use peptibodyF2 as a delivery vehicle for cytotoxic drugs, we have conjugated it with MMAE, a drug widely used in antibody-drug conjugates for targeted therapy. Resulting conjugate shows high and specific cytotoxicity towards FGFR1-positive cells, i.e., squamous cell lung carcinoma NCI-H520, while remaining non-toxic for FGFR1-negative cells. Such peptibody-drug conjugate can serve as a basis for development of therapy for tumors with overexpressed or malfunctioning FGFRs.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12102992