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Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures

Ad5-delta-24-RGD is currently the most clinically advanced recombinant adenovirus (rAd) for glioma therapy. We constructed a panel of fiber-modified rAds (Ad5RGD, Ad5/3, Ad5/35, Ad5/3RGD, and Ad5/35RGD, all harboring the delta-24 modification) and compared their infectivity, replication, reproductio...

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Autores principales: Stepanenko, Aleksei A., Sosnovtseva, Anastasiia O., Valikhov, Marat P., Chernysheva, Anastasia A., Cherepanov, Sergey A., Yusubalieva, Gaukhar M., Ruzsics, Zsolt, Lipatova, Anastasiia V., Chekhonin, Vladimir P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761956/
https://www.ncbi.nlm.nih.gov/pubmed/35071746
http://dx.doi.org/10.1016/j.omto.2021.12.013
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author Stepanenko, Aleksei A.
Sosnovtseva, Anastasiia O.
Valikhov, Marat P.
Chernysheva, Anastasia A.
Cherepanov, Sergey A.
Yusubalieva, Gaukhar M.
Ruzsics, Zsolt
Lipatova, Anastasiia V.
Chekhonin, Vladimir P.
author_facet Stepanenko, Aleksei A.
Sosnovtseva, Anastasiia O.
Valikhov, Marat P.
Chernysheva, Anastasia A.
Cherepanov, Sergey A.
Yusubalieva, Gaukhar M.
Ruzsics, Zsolt
Lipatova, Anastasiia V.
Chekhonin, Vladimir P.
author_sort Stepanenko, Aleksei A.
collection PubMed
description Ad5-delta-24-RGD is currently the most clinically advanced recombinant adenovirus (rAd) for glioma therapy. We constructed a panel of fiber-modified rAds (Ad5RGD, Ad5/3, Ad5/35, Ad5/3RGD, and Ad5/35RGD, all harboring the delta-24 modification) and compared their infectivity, replication, reproduction, and cytolytic efficacy in human and rodent glioma cell lines and short-term cultures from primary gliomas. In human cells, both Ad5/35-delta-24 and Ad5/3-delta-24 displayed superior infectivity and cytolytic efficacy over Ad5-delta-24-RGD, while Ad5/3-delta-24-RGD and Ad5/35-delta-24-RGD did not show further improvements in efficacy. The expression of the adenoviral receptors/coreceptors CAR, DSG2, and CD46 and the integrins αVβ3/αVβ5 did not predict the relative cytolytic efficacy of the fiber-modified rAds. The cytotoxicity of the fiber-modified rAds in human primary normal cultures of different origins and in primary glioma cultures was comparable, indicating that the delta-24 modification did not confer tumor cell selectivity. We also revealed that CT-2A and GL261 glioma cells might be used as murine cell models for the fiber chimeric rAds in vitro and in vivo. In GL261 tumor-bearing mice, Ad5/35-delta-24, armed with the immune costimulator OX40L as the E2A/DBP-p2A-mOX40L fusion, produced long-term survivors, which were able to reject tumor cells upon rechallenge. Our data underscore the potential of local Ad5/35-delta-24-based immunovirotherapy for glioblastoma treatment.
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spelling pubmed-87619562022-01-21 Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures Stepanenko, Aleksei A. Sosnovtseva, Anastasiia O. Valikhov, Marat P. Chernysheva, Anastasia A. Cherepanov, Sergey A. Yusubalieva, Gaukhar M. Ruzsics, Zsolt Lipatova, Anastasiia V. Chekhonin, Vladimir P. Mol Ther Oncolytics Original Article Ad5-delta-24-RGD is currently the most clinically advanced recombinant adenovirus (rAd) for glioma therapy. We constructed a panel of fiber-modified rAds (Ad5RGD, Ad5/3, Ad5/35, Ad5/3RGD, and Ad5/35RGD, all harboring the delta-24 modification) and compared their infectivity, replication, reproduction, and cytolytic efficacy in human and rodent glioma cell lines and short-term cultures from primary gliomas. In human cells, both Ad5/35-delta-24 and Ad5/3-delta-24 displayed superior infectivity and cytolytic efficacy over Ad5-delta-24-RGD, while Ad5/3-delta-24-RGD and Ad5/35-delta-24-RGD did not show further improvements in efficacy. The expression of the adenoviral receptors/coreceptors CAR, DSG2, and CD46 and the integrins αVβ3/αVβ5 did not predict the relative cytolytic efficacy of the fiber-modified rAds. The cytotoxicity of the fiber-modified rAds in human primary normal cultures of different origins and in primary glioma cultures was comparable, indicating that the delta-24 modification did not confer tumor cell selectivity. We also revealed that CT-2A and GL261 glioma cells might be used as murine cell models for the fiber chimeric rAds in vitro and in vivo. In GL261 tumor-bearing mice, Ad5/35-delta-24, armed with the immune costimulator OX40L as the E2A/DBP-p2A-mOX40L fusion, produced long-term survivors, which were able to reject tumor cells upon rechallenge. Our data underscore the potential of local Ad5/35-delta-24-based immunovirotherapy for glioblastoma treatment. American Society of Gene & Cell Therapy 2021-12-21 /pmc/articles/PMC8761956/ /pubmed/35071746 http://dx.doi.org/10.1016/j.omto.2021.12.013 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Stepanenko, Aleksei A.
Sosnovtseva, Anastasiia O.
Valikhov, Marat P.
Chernysheva, Anastasia A.
Cherepanov, Sergey A.
Yusubalieva, Gaukhar M.
Ruzsics, Zsolt
Lipatova, Anastasiia V.
Chekhonin, Vladimir P.
Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures
title Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures
title_full Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures
title_fullStr Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures
title_full_unstemmed Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures
title_short Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures
title_sort superior infectivity of the fiber chimeric oncolytic adenoviruses ad5/35 and ad5/3 over ad5-delta-24-rgd in primary glioma cultures
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761956/
https://www.ncbi.nlm.nih.gov/pubmed/35071746
http://dx.doi.org/10.1016/j.omto.2021.12.013
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