A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients

Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its...

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Authors: García Martin, Margarita, Moreno Olié, Rafael, Gil-Martín, Marta, Cascallò, Manel, Ochoa de Olza, Maria, Cuadra, Carmen, Piulats, Josep M., Navarro-Pérez, Valentin, Domenech, Marta, Alemany Bonastre, Ramon, Salazar Soler, Ramón
Format: article
Status:Versión aceptada para publicación
Publication Date:2018
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/128524
Online Access:https://hdl.handle.net/2445/128524
Access Level:Open access
Keyword:Melanoma
Virus oncogènics
Herpes
Oncogenic viruses
Herpesvirus diseases
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spelling A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patientsGarcía Martin, MargaritaMoreno Olié, RafaelGil-Martín, MartaCascallò, ManelOchoa de Olza, MariaCuadra, CarmenPiulats, Josep M.Navarro-Pérez, ValentinDomenech, MartaAlemany Bonastre, RamonSalazar Soler, RamónMelanomaVirus oncogènicsHerpesOncogenic virusesHerpesvirus diseasesOncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in the United States and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the retinoblastoma pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase 1 trial in metastatic melanoma patients. The results in 12 patients treated with a single infusion of a dose up to 1 × 1013 viral particles show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer.Mary Ann Liebert, Inc.201920192018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/2445/128524Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: http://dx.doi.org/10.1089/hum.2018.107http://dx.doi.org/10.1089/hum.2018.107(c) Mary Ann Liebert, Inc., 2019info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1285242026-05-29T05:05:01Z
dc.title.none.fl_str_mv A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients
title A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients
spellingShingle A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients
García Martin, Margarita
Melanoma
Virus oncogènics
Herpes
Oncogenic viruses
Herpesvirus diseases
title_short A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients
title_full A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients
title_fullStr A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients
title_full_unstemmed A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients
title_sort A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients
dc.creator.none.fl_str_mv García Martin, Margarita
Moreno Olié, Rafael
Gil-Martín, Marta
Cascallò, Manel
Ochoa de Olza, Maria
Cuadra, Carmen
Piulats, Josep M.
Navarro-Pérez, Valentin
Domenech, Marta
Alemany Bonastre, Ramon
Salazar Soler, Ramón
author García Martin, Margarita
author_facet García Martin, Margarita
Moreno Olié, Rafael
Gil-Martín, Marta
Cascallò, Manel
Ochoa de Olza, Maria
Cuadra, Carmen
Piulats, Josep M.
Navarro-Pérez, Valentin
Domenech, Marta
Alemany Bonastre, Ramon
Salazar Soler, Ramón
author_role author
author2 Moreno Olié, Rafael
Gil-Martín, Marta
Cascallò, Manel
Ochoa de Olza, Maria
Cuadra, Carmen
Piulats, Josep M.
Navarro-Pérez, Valentin
Domenech, Marta
Alemany Bonastre, Ramon
Salazar Soler, Ramón
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Melanoma
Virus oncogènics
Herpes
Oncogenic viruses
Herpesvirus diseases
topic Melanoma
Virus oncogènics
Herpes
Oncogenic viruses
Herpesvirus diseases
description Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in the United States and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the retinoblastoma pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase 1 trial in metastatic melanoma patients. The results in 12 patients treated with a single infusion of a dose up to 1 × 1013 viral particles show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/128524
url https://hdl.handle.net/2445/128524
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: http://dx.doi.org/10.1089/hum.2018.107
http://dx.doi.org/10.1089/hum.2018.107
dc.rights.none.fl_str_mv (c) Mary Ann Liebert, Inc., 2019
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Mary Ann Liebert, Inc., 2019
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Mary Ann Liebert, Inc.
publisher.none.fl_str_mv Mary Ann Liebert, Inc.
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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