Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy
Objective: Tumor necrosis factor-alpha (TNF-α), checkpoint inhibitors, and interleukin-17 (IL-17) are critical targets in inflammation and autoimmune diseases. Monoclonal antibodies (mAbs) have a successful portfolio in the treatment of chronic diseases. With the current progress in stem cells and...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Royan Institute (ACECR), Tehran
2019-08-01
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| Series: | Cell Journal |
| Subjects: | |
| Online Access: | https://celljournal.org/journal/article/fulltext/biosimilar-gene-therapy-investigational-assessment-of-secukinumab-gene-therapy.pdf |
| _version_ | 1818176290747842560 |
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| author | Ali Fallah Hajar Estiri Elizabeth Parrish Mansoureh Soleimani Sirous Zeinali Azita Zadeh-Vakili |
| author_facet | Ali Fallah Hajar Estiri Elizabeth Parrish Mansoureh Soleimani Sirous Zeinali Azita Zadeh-Vakili |
| author_sort | Ali Fallah |
| collection | DOAJ |
| description | Objective: Tumor necrosis factor-alpha (TNF-α), checkpoint inhibitors, and interleukin-17 (IL-17) are critical targets in
inflammation and autoimmune diseases. Monoclonal antibodies (mAbs) have a successful portfolio in the treatment of chronic
diseases. With the current progress in stem cells and gene therapy technologies, there is the promise of replacing costly mAbs
production in bioreactors with a more direct and cost-effective production method inside the patient’s cells. In this paper we
examine the results of an investigational assessment of secukinumab gene therapy.
Materials and Methods: In this experimental study, the DNA sequence of the heavy and light chains of secukinumab
antibodies were cloned in a lentiviral vector. Human chorionic villous mesenchymal stem cells (CMSCs) were isolated and
characterized. After lentiviral packaging and titration, part of the recombinant viruses was used for transduction of the CMSCs
and the other part were applied for systemic gene therapy. The engineered stem cells and recombinant viruses were applied
for ex vivo and in vivo gene therapy, respectively, in different groups of rat models. In vitro and in vivo secukinumab expression
was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and ELISA by considering the
approved secukinumab as the standard reference.
Results: Cell differentiation assays and flow cytometry of standard biomarkers confirmed the multipotency of the
CMSCs. Western blot and qRT-PCR confirmed in vitro gene expression of secukinumab at both the mRNA and protein
level. ELISA testing of serum from treated rat models confirmed mAb overexpression for both in vivo and ex vivo gene
therapies.
Conclusion: In this study, a lentiviral-mediated ex vivo and in vivo gene therapy was developed to provide a moderate dose
of secukinumab in rat models. Biosimilar gene therapy is an attractive approach for the treatment of autoimmune disorders,
cancers and other chronic diseases. |
| first_indexed | 2024-12-11T20:13:51Z |
| format | Article |
| id | doaj.art-750a914d493041649600e86852dba901 |
| institution | Directory Open Access Journal |
| issn | 2228-5806 2228-5814 |
| language | English |
| last_indexed | 2024-12-11T20:13:51Z |
| publishDate | 2019-08-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj.art-750a914d493041649600e86852dba9012022-12-22T00:52:14ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142019-08-0121443344310.22074/cellj.2020.6309Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene TherapyAli Fallah0Hajar Estiri1Elizabeth Parrish2Mansoureh Soleimani3Sirous Zeinali4Azita Zadeh-Vakili5Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranRNAx Ltd., London, UKRNAx Ltd., London, UKCellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, IranMolecular Medicine, Pasteur Institute of Iran, Tehran, IranCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IranObjective: Tumor necrosis factor-alpha (TNF-α), checkpoint inhibitors, and interleukin-17 (IL-17) are critical targets in inflammation and autoimmune diseases. Monoclonal antibodies (mAbs) have a successful portfolio in the treatment of chronic diseases. With the current progress in stem cells and gene therapy technologies, there is the promise of replacing costly mAbs production in bioreactors with a more direct and cost-effective production method inside the patient’s cells. In this paper we examine the results of an investigational assessment of secukinumab gene therapy. Materials and Methods: In this experimental study, the DNA sequence of the heavy and light chains of secukinumab antibodies were cloned in a lentiviral vector. Human chorionic villous mesenchymal stem cells (CMSCs) were isolated and characterized. After lentiviral packaging and titration, part of the recombinant viruses was used for transduction of the CMSCs and the other part were applied for systemic gene therapy. The engineered stem cells and recombinant viruses were applied for ex vivo and in vivo gene therapy, respectively, in different groups of rat models. In vitro and in vivo secukinumab expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and ELISA by considering the approved secukinumab as the standard reference. Results: Cell differentiation assays and flow cytometry of standard biomarkers confirmed the multipotency of the CMSCs. Western blot and qRT-PCR confirmed in vitro gene expression of secukinumab at both the mRNA and protein level. ELISA testing of serum from treated rat models confirmed mAb overexpression for both in vivo and ex vivo gene therapies. Conclusion: In this study, a lentiviral-mediated ex vivo and in vivo gene therapy was developed to provide a moderate dose of secukinumab in rat models. Biosimilar gene therapy is an attractive approach for the treatment of autoimmune disorders, cancers and other chronic diseases.https://celljournal.org/journal/article/fulltext/biosimilar-gene-therapy-investigational-assessment-of-secukinumab-gene-therapy.pdfGene TherapyGenetic VectorsMonoclonal AntibodySecukinumabStem Cells |
| spellingShingle | Ali Fallah Hajar Estiri Elizabeth Parrish Mansoureh Soleimani Sirous Zeinali Azita Zadeh-Vakili Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy Cell Journal Gene Therapy Genetic Vectors Monoclonal Antibody Secukinumab Stem Cells |
| title | Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy |
| title_full | Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy |
| title_fullStr | Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy |
| title_full_unstemmed | Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy |
| title_short | Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy |
| title_sort | biosimilar gene therapy investigational assessment of secukinumab gene therapy |
| topic | Gene Therapy Genetic Vectors Monoclonal Antibody Secukinumab Stem Cells |
| url | https://celljournal.org/journal/article/fulltext/biosimilar-gene-therapy-investigational-assessment-of-secukinumab-gene-therapy.pdf |
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