Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting

Autores
Villaverde, Marcela Solange; Combe, Kristell; Duchene, Adriana Graciela; Wei, Ming X; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In an aggressive B16-F10 murine melanoma model, we evaluated the effectiveness and antitumor mechanisms triggered by a surgery adjuvant treatment that combined a local suicide gene therapy (SG) with a subcutaneous genetic vaccine (Vx) composed by B16-F10 cell extracts and lipoplexes carrying the genes of human interleukin-2 and murine granulocyte and macrophage colony stimulating factor. Pre-surgical SG treatment, neither alone nor combined with Vx was able to slow down the fast evolution of this tumor. After surgery, both SG and SG+Vx treatments, significantly prevented (in 50 % of mice) or delayed (in the remaining 50 %) post-surgical recurrence, as well as significantly prolonged recurrence-free (SG and SG+Vx) and overall median survival (SG+Vx). The treatment induced the generation of a pseudocapsule wrapping and separating the tumor from surrounding host tissue. Both, SG and the subcutaneous Vx, induced this envelope that was absent in the control group. On the other hand, PET scan imaging of SG+Vx group suggested the development of an effective systemic immunostimulation that enhanced 18FDG accrual in thymus, spleen and vertebral column. When combined to surgery, direct intralesional injection of suicide gene plus distal subcutaneous genetic vaccine displayed efficacy and systemic antitumor immune response without host toxicity. This suggests the potential value of the assayed approach for clinical purposes.
Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina
Fil: Combe, Kristell. École Nationale Vétérinaire d'Alfort; Francia
Fil: Duchene, Adriana Graciela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Wei, Ming X. École Nationale Vétérinaire d'Alfort; Francia
Fil: Glikin, Gerardo Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina
Fil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
IL-2
GM-CSF
melanoma vaccine
HSV-TK
PET/Scan
lipofection
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/106795
Acceder
id CONICETDig_8d2c0142a13675522d11396680dde893
oai_identifier_str oai:ri.conicet.gov.ar:11336/106795
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma settingVillaverde, Marcela SolangeCombe, KristellDuchene, Adriana GracielaWei, Ming XGlikin, Gerardo ClaudioFinocchiaro, Liliana Maria ElenaIL-2GM-CSFmelanoma vaccineHSV-TKPET/Scanlipofectionhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3In an aggressive B16-F10 murine melanoma model, we evaluated the effectiveness and antitumor mechanisms triggered by a surgery adjuvant treatment that combined a local suicide gene therapy (SG) with a subcutaneous genetic vaccine (Vx) composed by B16-F10 cell extracts and lipoplexes carrying the genes of human interleukin-2 and murine granulocyte and macrophage colony stimulating factor. Pre-surgical SG treatment, neither alone nor combined with Vx was able to slow down the fast evolution of this tumor. After surgery, both SG and SG+Vx treatments, significantly prevented (in 50 % of mice) or delayed (in the remaining 50 %) post-surgical recurrence, as well as significantly prolonged recurrence-free (SG and SG+Vx) and overall median survival (SG+Vx). The treatment induced the generation of a pseudocapsule wrapping and separating the tumor from surrounding host tissue. Both, SG and the subcutaneous Vx, induced this envelope that was absent in the control group. On the other hand, PET scan imaging of SG+Vx group suggested the development of an effective systemic immunostimulation that enhanced 18FDG accrual in thymus, spleen and vertebral column. When combined to surgery, direct intralesional injection of suicide gene plus distal subcutaneous genetic vaccine displayed efficacy and systemic antitumor immune response without host toxicity. This suggests the potential value of the assayed approach for clinical purposes.Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; ArgentinaFil: Combe, Kristell. École Nationale Vétérinaire d'Alfort; FranciaFil: Duchene, Adriana Graciela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Wei, Ming X. École Nationale Vétérinaire d'Alfort; FranciaFil: Glikin, Gerardo Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; ArgentinaFil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Science2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/106795Villaverde, Marcela Solange; Combe, Kristell; Duchene, Adriana Graciela; Wei, Ming X; Glikin, Gerardo Claudio; et al.; Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting; Elsevier Science; International Immunopharmacology; 22; 1; 9-2014; 167-1751567-5769CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1567576914002355info:eu-repo/semantics/altIdentifier/doi/10.1016/j.intimp.2014.06.021info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:02:18Zoai:ri.conicet.gov.ar:11336/106795instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:02:18.591CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting
title Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting
spellingShingle Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting
Villaverde, Marcela Solange
IL-2
GM-CSF
melanoma vaccine
HSV-TK
PET/Scan
lipofection
title_short Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting
title_full Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting
title_fullStr Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting
title_full_unstemmed Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting
title_sort Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting
dc.creator.none.fl_str_mv Villaverde, Marcela Solange
Combe, Kristell
Duchene, Adriana Graciela
Wei, Ming X
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
author Villaverde, Marcela Solange
author_facet Villaverde, Marcela Solange
Combe, Kristell
Duchene, Adriana Graciela
Wei, Ming X
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
author_role author
author2 Combe, Kristell
Duchene, Adriana Graciela
Wei, Ming X
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv IL-2
GM-CSF
melanoma vaccine
HSV-TK
PET/Scan
lipofection
topic IL-2
GM-CSF
melanoma vaccine
HSV-TK
PET/Scan
lipofection
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In an aggressive B16-F10 murine melanoma model, we evaluated the effectiveness and antitumor mechanisms triggered by a surgery adjuvant treatment that combined a local suicide gene therapy (SG) with a subcutaneous genetic vaccine (Vx) composed by B16-F10 cell extracts and lipoplexes carrying the genes of human interleukin-2 and murine granulocyte and macrophage colony stimulating factor. Pre-surgical SG treatment, neither alone nor combined with Vx was able to slow down the fast evolution of this tumor. After surgery, both SG and SG+Vx treatments, significantly prevented (in 50 % of mice) or delayed (in the remaining 50 %) post-surgical recurrence, as well as significantly prolonged recurrence-free (SG and SG+Vx) and overall median survival (SG+Vx). The treatment induced the generation of a pseudocapsule wrapping and separating the tumor from surrounding host tissue. Both, SG and the subcutaneous Vx, induced this envelope that was absent in the control group. On the other hand, PET scan imaging of SG+Vx group suggested the development of an effective systemic immunostimulation that enhanced 18FDG accrual in thymus, spleen and vertebral column. When combined to surgery, direct intralesional injection of suicide gene plus distal subcutaneous genetic vaccine displayed efficacy and systemic antitumor immune response without host toxicity. This suggests the potential value of the assayed approach for clinical purposes.
Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina
Fil: Combe, Kristell. École Nationale Vétérinaire d'Alfort; Francia
Fil: Duchene, Adriana Graciela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Wei, Ming X. École Nationale Vétérinaire d'Alfort; Francia
Fil: Glikin, Gerardo Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina
Fil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description In an aggressive B16-F10 murine melanoma model, we evaluated the effectiveness and antitumor mechanisms triggered by a surgery adjuvant treatment that combined a local suicide gene therapy (SG) with a subcutaneous genetic vaccine (Vx) composed by B16-F10 cell extracts and lipoplexes carrying the genes of human interleukin-2 and murine granulocyte and macrophage colony stimulating factor. Pre-surgical SG treatment, neither alone nor combined with Vx was able to slow down the fast evolution of this tumor. After surgery, both SG and SG+Vx treatments, significantly prevented (in 50 % of mice) or delayed (in the remaining 50 %) post-surgical recurrence, as well as significantly prolonged recurrence-free (SG and SG+Vx) and overall median survival (SG+Vx). The treatment induced the generation of a pseudocapsule wrapping and separating the tumor from surrounding host tissue. Both, SG and the subcutaneous Vx, induced this envelope that was absent in the control group. On the other hand, PET scan imaging of SG+Vx group suggested the development of an effective systemic immunostimulation that enhanced 18FDG accrual in thymus, spleen and vertebral column. When combined to surgery, direct intralesional injection of suicide gene plus distal subcutaneous genetic vaccine displayed efficacy and systemic antitumor immune response without host toxicity. This suggests the potential value of the assayed approach for clinical purposes.
publishDate 2014
dc.date.none.fl_str_mv 2014-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/106795
Villaverde, Marcela Solange; Combe, Kristell; Duchene, Adriana Graciela; Wei, Ming X; Glikin, Gerardo Claudio; et al.; Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting; Elsevier Science; International Immunopharmacology; 22; 1; 9-2014; 167-175
1567-5769
CONICET Digital
CONICET
url http://hdl.handle.net/11336/106795
identifier_str_mv Villaverde, Marcela Solange; Combe, Kristell; Duchene, Adriana Graciela; Wei, Ming X; Glikin, Gerardo Claudio; et al.; Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting; Elsevier Science; International Immunopharmacology; 22; 1; 9-2014; 167-175
1567-5769
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1567576914002355
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.intimp.2014.06.021
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842980007925776384
score 13.004268

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