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Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug

AIM: Immunotoxins are proteins that consist of an antibody fragment linked to a toxin, used as agents for targeted therapy of cancers. Although the most potent immunotoxins are made from bacterial and plant toxins, obstacles which contribute to poor responses are immunogenicity in patients and rapid...

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Detalles Bibliográficos
Autores principales: Bemani, Peyman, Mohammadi, Mozafar, Hakakian, Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844643/
https://www.ncbi.nlm.nih.gov/pubmed/29373898
http://dx.doi.org/10.22034/APJCP.2018.19.1.97
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author Bemani, Peyman
Mohammadi, Mozafar
Hakakian, Ali
author_facet Bemani, Peyman
Mohammadi, Mozafar
Hakakian, Ali
author_sort Bemani, Peyman
collection PubMed
description AIM: Immunotoxins are proteins that consist of an antibody fragment linked to a toxin, used as agents for targeted therapy of cancers. Although the most potent immunotoxins are made from bacterial and plant toxins, obstacles which contribute to poor responses are immunogenicity in patients and rapid development of neutralizing antibodies. In the present study we proposed a new therapeutic immunotoxin for targeted cancer therapy of ROR1 expressing cancers: an anti ROR1 single chain fragment variable antibody (scFv)-endonuclease G (anti ROR1 scFv-EndoG). METHODS: The three-dimensional structure of anti ROR1 scFv-EndoG protein was modeled and structure validation tools were employed to confirm the accuracy and reliability of the developed model. In addition, stability and integrity of the model were assessed by molecular dynamic (MD) simulation. RESULTS: All results suggested the protein model to be acceptable and of good quality. CONCLUSIONS: Anti-ROR1 scFv-EndoG would be expected to bind to the ROR1 extracellular domain by its scFv portion and selectively deliver non-immunogenic human endonuclease G enzyme as an end-stage apoptosis molecule into ROR1-expressing cancer cells and lead rapidly to apoptosis. We believe that anti ROR1 and other anti-tumor antigen scFv-EndoG forms may be helpful for cancer therapy.
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spelling pubmed-58446432018-03-20 Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug Bemani, Peyman Mohammadi, Mozafar Hakakian, Ali Asian Pac J Cancer Prev Research Article AIM: Immunotoxins are proteins that consist of an antibody fragment linked to a toxin, used as agents for targeted therapy of cancers. Although the most potent immunotoxins are made from bacterial and plant toxins, obstacles which contribute to poor responses are immunogenicity in patients and rapid development of neutralizing antibodies. In the present study we proposed a new therapeutic immunotoxin for targeted cancer therapy of ROR1 expressing cancers: an anti ROR1 single chain fragment variable antibody (scFv)-endonuclease G (anti ROR1 scFv-EndoG). METHODS: The three-dimensional structure of anti ROR1 scFv-EndoG protein was modeled and structure validation tools were employed to confirm the accuracy and reliability of the developed model. In addition, stability and integrity of the model were assessed by molecular dynamic (MD) simulation. RESULTS: All results suggested the protein model to be acceptable and of good quality. CONCLUSIONS: Anti-ROR1 scFv-EndoG would be expected to bind to the ROR1 extracellular domain by its scFv portion and selectively deliver non-immunogenic human endonuclease G enzyme as an end-stage apoptosis molecule into ROR1-expressing cancer cells and lead rapidly to apoptosis. We believe that anti ROR1 and other anti-tumor antigen scFv-EndoG forms may be helpful for cancer therapy. West Asia Organization for Cancer Prevention 2018 /pmc/articles/PMC5844643/ /pubmed/29373898 http://dx.doi.org/10.22034/APJCP.2018.19.1.97 Text en Copyright: © Asian Pacific Journal of Cancer Prevention http://creativecommons.org/licenses/BY-SA/4.0 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
spellingShingle Research Article
Bemani, Peyman
Mohammadi, Mozafar
Hakakian, Ali
Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug
title Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug
title_full Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug
title_fullStr Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug
title_full_unstemmed Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug
title_short Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug
title_sort anti-ror1 scfv-endog as a novel anti-cancer therapeutic drug
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844643/
https://www.ncbi.nlm.nih.gov/pubmed/29373898
http://dx.doi.org/10.22034/APJCP.2018.19.1.97
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