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

Aleksei A. Stepanenko; Anastasiia O. Sosnovtseva; Marat P. Valikhov; Anastasia A. Chernysheva; Sergey A. Cherepanov; Gaukhar M. Yusubalieva; Zsolt Ruzsics; Anastasiia V. Lipatova; Vladimir P. Chekhonin

Molecular Therapy: Oncolytics (Mar 2022)

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

Aleksei A. Stepanenko,
Anastasiia O. Sosnovtseva,
Marat P. Valikhov,
Anastasia A. Chernysheva,
Sergey A. Cherepanov,
Gaukhar M. Yusubalieva,
Zsolt Ruzsics,
Anastasiia V. Lipatova,
Vladimir P. Chekhonin

Affiliations

Aleksei A. Stepanenko: Department of Fundamental and Applied Neurobiology, V.P. Serbsky National Medical Research Center of Psychiatry and Narcology, The Ministry of Health of the Russian Federation, Kropotkinsky Lane 23, 119034 Moscow, Russia; Department of Medical Nanobiotechnology, Institute of Translational Medicine, N.I. Pirogov Russian National Research Medical University, The Ministry of Health of the Russian Federation, Ostrovitianov Str. 1, 117997 Moscow, Russia; Corresponding author Aleksei A. Stepanenko, Department of Fundamental and Applied Neurobiology, V.P. Serbsky National Medical Research Center of Psychiatry and Narcology, The Ministry of Health of the Russian Federation, Kropotkinsky Lane 23, 119034 Moscow, Russia.
Anastasiia O. Sosnovtseva: Department of Fundamental and Applied Neurobiology, V.P. Serbsky National Medical Research Center of Psychiatry and Narcology, The Ministry of Health of the Russian Federation, Kropotkinsky Lane 23, 119034 Moscow, Russia
Marat P. Valikhov: Department of Fundamental and Applied Neurobiology, V.P. Serbsky National Medical Research Center of Psychiatry and Narcology, The Ministry of Health of the Russian Federation, Kropotkinsky Lane 23, 119034 Moscow, Russia; Department of Medical Nanobiotechnology, Institute of Translational Medicine, N.I. Pirogov Russian National Research Medical University, The Ministry of Health of the Russian Federation, Ostrovitianov Str. 1, 117997 Moscow, Russia
Anastasia A. Chernysheva: Department of Fundamental and Applied Neurobiology, V.P. Serbsky National Medical Research Center of Psychiatry and Narcology, The Ministry of Health of the Russian Federation, Kropotkinsky Lane 23, 119034 Moscow, Russia
Sergey A. Cherepanov: Department of Fundamental and Applied Neurobiology, V.P. Serbsky National Medical Research Center of Psychiatry and Narcology, The Ministry of Health of the Russian Federation, Kropotkinsky Lane 23, 119034 Moscow, Russia
Gaukhar M. Yusubalieva: Federal Research and Clinical Center for Specialized Types of Medical Care and Medical Technologies of the FMBA of Russia, Moscow, Russia
Zsolt Ruzsics: Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
Anastasiia V. Lipatova: Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
Vladimir P. Chekhonin: Department of Fundamental and Applied Neurobiology, V.P. Serbsky National Medical Research Center of Psychiatry and Narcology, The Ministry of Health of the Russian Federation, Kropotkinsky Lane 23, 119034 Moscow, Russia; Department of Medical Nanobiotechnology, Institute of Translational Medicine, N.I. Pirogov Russian National Research Medical University, The Ministry of Health of the Russian Federation, Ostrovitianov Str. 1, 117997 Moscow, Russia

Journal volume & issue: Vol. 24
pp. 230 – 248

Abstract

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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.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

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