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Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1
In our previous work we demonstrated that a small protein called affibody can be used for a cytotoxic conjugate development. The anti-HER2 affibody was armed with one moiety of a highly potent auristatin E and specifically killed HER2-positive cancer cells with a nanomolar IC(50). The aim of this st...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578078/ https://www.ncbi.nlm.nih.gov/pubmed/28771178 http://dx.doi.org/10.3390/ijms18081688 |
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author | Sochaj-Gregorczyk, Alicja M. Ludzia, Patryk Kozdrowska, Emilia Jakimowicz, Piotr Sokolowska-Wedzina, Aleksandra Otlewski, Jacek |
author_facet | Sochaj-Gregorczyk, Alicja M. Ludzia, Patryk Kozdrowska, Emilia Jakimowicz, Piotr Sokolowska-Wedzina, Aleksandra Otlewski, Jacek |
author_sort | Sochaj-Gregorczyk, Alicja M. |
collection | PubMed |
description | In our previous work we demonstrated that a small protein called affibody can be used for a cytotoxic conjugate development. The anti-HER2 affibody was armed with one moiety of a highly potent auristatin E and specifically killed HER2-positive cancer cells with a nanomolar IC(50). The aim of this study was to improve the anti-HER2 affibody conjugate by increasing its size and the number of conjugated auristatin molecules. The affibody was fused to the Fc fragment of IgG1 resulting in a dimeric construct with the molecular weight of 68 kDa, referred to as Z(HER2:2891)-Fc, ensuring its prolonged half-life in the blood. Due to the presence of four interchain cysteines, the fusion protein could carry four drug molecules. Notably, the in vitro tests of the improved anti-HER2 conjugate revealed that it exhibits the IC(50) of 130 pM for the HER2-positive SK-BR-3 cells and 98 nM for the HER2-negative MDA-MB-231 cells. High efficacy and specificity of the auristatin conjugate based on Z(HER2:2891)-Fc indicate that this construct is suitable for further in vivo evaluation. |
format | Online Article Text |
id | pubmed-5578078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-55780782017-09-05 Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1 Sochaj-Gregorczyk, Alicja M. Ludzia, Patryk Kozdrowska, Emilia Jakimowicz, Piotr Sokolowska-Wedzina, Aleksandra Otlewski, Jacek Int J Mol Sci Article In our previous work we demonstrated that a small protein called affibody can be used for a cytotoxic conjugate development. The anti-HER2 affibody was armed with one moiety of a highly potent auristatin E and specifically killed HER2-positive cancer cells with a nanomolar IC(50). The aim of this study was to improve the anti-HER2 affibody conjugate by increasing its size and the number of conjugated auristatin molecules. The affibody was fused to the Fc fragment of IgG1 resulting in a dimeric construct with the molecular weight of 68 kDa, referred to as Z(HER2:2891)-Fc, ensuring its prolonged half-life in the blood. Due to the presence of four interchain cysteines, the fusion protein could carry four drug molecules. Notably, the in vitro tests of the improved anti-HER2 conjugate revealed that it exhibits the IC(50) of 130 pM for the HER2-positive SK-BR-3 cells and 98 nM for the HER2-negative MDA-MB-231 cells. High efficacy and specificity of the auristatin conjugate based on Z(HER2:2891)-Fc indicate that this construct is suitable for further in vivo evaluation. MDPI 2017-08-03 /pmc/articles/PMC5578078/ /pubmed/28771178 http://dx.doi.org/10.3390/ijms18081688 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sochaj-Gregorczyk, Alicja M. Ludzia, Patryk Kozdrowska, Emilia Jakimowicz, Piotr Sokolowska-Wedzina, Aleksandra Otlewski, Jacek Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1 |
title | Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1 |
title_full | Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1 |
title_fullStr | Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1 |
title_full_unstemmed | Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1 |
title_short | Design and In Vitro Evaluation of a Cytotoxic Conjugate Based on the Anti-HER2 Affibody Fused to the Fc Fragment of IgG1 |
title_sort | design and in vitro evaluation of a cytotoxic conjugate based on the anti-her2 affibody fused to the fc fragment of igg1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578078/ https://www.ncbi.nlm.nih.gov/pubmed/28771178 http://dx.doi.org/10.3390/ijms18081688 |
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