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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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/10/2992 |
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| author | Karolina Jendryczko Julia Chudzian Natalia Skinder Łukasz Opaliński Jakub Rzeszótko Antoni Wiedlocha Jacek Otlewski Anna Szlachcic |
| author_facet | Karolina Jendryczko Julia Chudzian Natalia Skinder Łukasz Opaliński Jakub Rzeszótko Antoni Wiedlocha Jacek Otlewski Anna Szlachcic |
| author_sort | Karolina Jendryczko |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T15:35:31Z |
| format | Article |
| id | doaj.art-623d1784c12b472793c80a5febc947c4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:35:31Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-623d1784c12b472793c80a5febc947c42023-11-20T17:15:42ZengMDPI AGCancers2072-66942020-10-011210299210.3390/cancers12102992FGF2-Derived PeptibodyF2-MMAE Conjugate for Targeted Delivery of Cytotoxic Drugs into Cancer Cells Overexpressing FGFR1Karolina Jendryczko0Julia Chudzian1Natalia Skinder2Łukasz Opaliński3Jakub Rzeszótko4Antoni Wiedlocha5Jacek Otlewski6Anna Szlachcic7Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50383 Wroclaw, PolandDepartment of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50383 Wroclaw, PolandDepartment of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50383 Wroclaw, PolandDepartment of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50383 Wroclaw, PolandDepartment of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50383 Wroclaw, PolandDepartment of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, NorwayDepartment of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50383 Wroclaw, PolandDepartment of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50383 Wroclaw, PolandFibroblast 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.https://www.mdpi.com/2072-6694/12/10/2992peptibodytargeted cancer therapyFGFRFGF2protein–drug conjugate |
| spellingShingle | Karolina Jendryczko Julia Chudzian Natalia Skinder Łukasz Opaliński Jakub Rzeszótko Antoni Wiedlocha Jacek Otlewski Anna Szlachcic FGF2-Derived PeptibodyF2-MMAE Conjugate for Targeted Delivery of Cytotoxic Drugs into Cancer Cells Overexpressing FGFR1 Cancers peptibody targeted cancer therapy FGFR FGF2 protein–drug conjugate |
| title | FGF2-Derived PeptibodyF2-MMAE Conjugate for Targeted Delivery of Cytotoxic Drugs into Cancer Cells Overexpressing FGFR1 |
| title_full | FGF2-Derived PeptibodyF2-MMAE Conjugate for Targeted Delivery of Cytotoxic Drugs into Cancer Cells Overexpressing FGFR1 |
| title_fullStr | FGF2-Derived PeptibodyF2-MMAE Conjugate for Targeted Delivery of Cytotoxic Drugs into Cancer Cells Overexpressing FGFR1 |
| title_full_unstemmed | FGF2-Derived PeptibodyF2-MMAE Conjugate for Targeted Delivery of Cytotoxic Drugs into Cancer Cells Overexpressing FGFR1 |
| title_short | FGF2-Derived PeptibodyF2-MMAE Conjugate for Targeted Delivery of Cytotoxic Drugs into Cancer Cells Overexpressing FGFR1 |
| title_sort | fgf2 derived peptibodyf2 mmae conjugate for targeted delivery of cytotoxic drugs into cancer cells overexpressing fgfr1 |
| topic | peptibody targeted cancer therapy FGFR FGF2 protein–drug conjugate |
| url | https://www.mdpi.com/2072-6694/12/10/2992 |
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