Formation of multimeric antibodies for self-delivery of active monomers
Proteins and peptides have been used as drugs for almost a century. Technological advances in the past 30 years have enabled the production of pure, stable proteins in vast amounts. In contrast, administration of proteins based on their native active conformation (and thus necessitating the use of s...
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doaj-32cd3e5bbae44058b79321327c98c2b52020-11-25T02:42:41ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642017-01-0124119920810.1080/10717544.2016.12421791242179Formation of multimeric antibodies for self-delivery of active monomersYaron Dekel0Yossy Machluf1Tal Gefen2Gennady Eidelshtein3Alexander Kotlyar4Yaron Bram5Ehud Shahar6Farah Reslane7Elina Aizenshtein8Jacob Pitcovski9Shamir Research Institute, University of HaifaConsultant, specialist in the fields of biochemistry, molecular biology and geneticsTel Hai CollegeDepartment of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, IsraelDepartment of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, IsraelTel Aviv UniversityTel Hai CollegeTel Hai CollegeTel Hai CollegeTel Hai CollegeProteins and peptides have been used as drugs for almost a century. Technological advances in the past 30 years have enabled the production of pure, stable proteins in vast amounts. In contrast, administration of proteins based on their native active conformation (and thus necessitating the use of subcutaneous injections) has remained solely unchanged. The therapeutic anti-HER2 humanized monoclonal immunoglobulin (IgG) Trastuzumab (Herceptin) is a first line of the treatment for breast cancer. Chicken IgY is a commercially important polyclonal antibody (Ab). These Abs were examined for their ability to self-assemble and form ordered aggregates, by several biophysical methods. Atomic force microscopy analyses revealed the formation of multimeric nanostructures. The biological activity of multimeric IgG or IgY particles was retained and restored, in a dilution/time-dependent manner. IgG activity was confirmed by a binding assay using HER2 + human breast cancer cell line, SKBR3, while IgY activity was confirmed by ELISA assay using the VP2 antigen. Competition assay with native Herceptin antibodies demonstrated that the binding availability of the multimer formulation remained unaffected. Under long incubation periods, IgG multimers retained five times more activity than native IgG. In conclusion, the multimeric antibody formulations can serve as a storage depositories and sustained-release particles. These two important characteristics make this formulation promising for future novel administration protocols and altogether bring to light a different conceptual approach for the future use of therapeutic proteins as self-delivery entities rather than conjugated/encapsulated to other bio-compounds.http://dx.doi.org/10.1080/10717544.2016.1242179protein drug releasebioactivityantibodiesmultimersself-delivery |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yaron Dekel Yossy Machluf Tal Gefen Gennady Eidelshtein Alexander Kotlyar Yaron Bram Ehud Shahar Farah Reslane Elina Aizenshtein Jacob Pitcovski |
spellingShingle |
Yaron Dekel Yossy Machluf Tal Gefen Gennady Eidelshtein Alexander Kotlyar Yaron Bram Ehud Shahar Farah Reslane Elina Aizenshtein Jacob Pitcovski Formation of multimeric antibodies for self-delivery of active monomers Drug Delivery protein drug release bioactivity antibodies multimers self-delivery |
author_facet |
Yaron Dekel Yossy Machluf Tal Gefen Gennady Eidelshtein Alexander Kotlyar Yaron Bram Ehud Shahar Farah Reslane Elina Aizenshtein Jacob Pitcovski |
author_sort |
Yaron Dekel |
title |
Formation of multimeric antibodies for self-delivery of active monomers |
title_short |
Formation of multimeric antibodies for self-delivery of active monomers |
title_full |
Formation of multimeric antibodies for self-delivery of active monomers |
title_fullStr |
Formation of multimeric antibodies for self-delivery of active monomers |
title_full_unstemmed |
Formation of multimeric antibodies for self-delivery of active monomers |
title_sort |
formation of multimeric antibodies for self-delivery of active monomers |
publisher |
Taylor & Francis Group |
series |
Drug Delivery |
issn |
1071-7544 1521-0464 |
publishDate |
2017-01-01 |
description |
Proteins and peptides have been used as drugs for almost a century. Technological advances in the past 30 years have enabled the production of pure, stable proteins in vast amounts. In contrast, administration of proteins based on their native active conformation (and thus necessitating the use of subcutaneous injections) has remained solely unchanged. The therapeutic anti-HER2 humanized monoclonal immunoglobulin (IgG) Trastuzumab (Herceptin) is a first line of the treatment for breast cancer. Chicken IgY is a commercially important polyclonal antibody (Ab). These Abs were examined for their ability to self-assemble and form ordered aggregates, by several biophysical methods. Atomic force microscopy analyses revealed the formation of multimeric nanostructures. The biological activity of multimeric IgG or IgY particles was retained and restored, in a dilution/time-dependent manner. IgG activity was confirmed by a binding assay using HER2 + human breast cancer cell line, SKBR3, while IgY activity was confirmed by ELISA assay using the VP2 antigen. Competition assay with native Herceptin antibodies demonstrated that the binding availability of the multimer formulation remained unaffected. Under long incubation periods, IgG multimers retained five times more activity than native IgG. In conclusion, the multimeric antibody formulations can serve as a storage depositories and sustained-release particles. These two important characteristics make this formulation promising for future novel administration protocols and altogether bring to light a different conceptual approach for the future use of therapeutic proteins as self-delivery entities rather than conjugated/encapsulated to other bio-compounds. |
topic |
protein drug release bioactivity antibodies multimers self-delivery |
url |
http://dx.doi.org/10.1080/10717544.2016.1242179 |
work_keys_str_mv |
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