Gene therapy for brain tumors: Basic developments and clinical implementation

Autores
Assi, Hikmat; Candolfi, Marianela; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro R.; Castro, Maria Gabriela
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Glioblastoma multiforme (GBM) is the most common and deadliest of adult primary brain tumors. Due to its invasive nature and sensitive location, complete resection remains virtually impossible. The resistance of GBM against chemotherapy and radiotherapy necessitate the development of novel therapies. Gene therapy is proposed for the treatment of brain tumors and has demonstrated pre-clinical efficacy in animal models. Here we review the various experimental therapies that have been developed for GBM including both cytotoxic and immune stimulatory approaches. We also review the combined conditional cytotoxic immune stimulatory therapy that our lab has developed which is dependent on the adenovirus mediated expression of the conditional cytotoxic gene, Herpes Simplex Type 1 Thymidine Kinase (TK) and the powerful DC growth factor Fms-like tyrosine kinase 3 ligand (Flt3L). Combined delivery of these vectors elicits tumor cell death and an anti-tumor adaptive immune response that requires TLR2 activation. The implications of our studies indicate that the combined cytotoxic and immunotherapeutic strategies are effective strategies to combat deadly brain tumors and warrant their implementation in human Phase I clinical trials for GBM. © 2012 Elsevier Ireland Ltd.
Fil: Assi, Hikmat. University of Michigan; Estados Unidos. David Geffen School of Medicine; Estados Unidos
Fil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Baker, Gregory. University of Michigan; Estados Unidos. David Geffen School of Medicine; Estados Unidos
Fil: Mineharu, Yohei. David Geffen School of Medicine; Estados Unidos
Fil: Lowenstein, Pedro R.. University of Michigan; Estados Unidos
Fil: Castro, Maria Gabriela. University of Michigan; Estados Unidos
Materia
Cytotoxic
Flt3l
Gene Therapy
Glioblastoma
Immunotherapy
Tk
Viral Vectors
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:11336/67290
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/67290
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Gene therapy for brain tumors: Basic developments and clinical implementationAssi, HikmatCandolfi, MarianelaBaker, GregoryMineharu, YoheiLowenstein, Pedro R.Castro, Maria GabrielaCytotoxicFlt3lGene TherapyGlioblastomaImmunotherapyTkViral Vectorshttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Glioblastoma multiforme (GBM) is the most common and deadliest of adult primary brain tumors. Due to its invasive nature and sensitive location, complete resection remains virtually impossible. The resistance of GBM against chemotherapy and radiotherapy necessitate the development of novel therapies. Gene therapy is proposed for the treatment of brain tumors and has demonstrated pre-clinical efficacy in animal models. Here we review the various experimental therapies that have been developed for GBM including both cytotoxic and immune stimulatory approaches. We also review the combined conditional cytotoxic immune stimulatory therapy that our lab has developed which is dependent on the adenovirus mediated expression of the conditional cytotoxic gene, Herpes Simplex Type 1 Thymidine Kinase (TK) and the powerful DC growth factor Fms-like tyrosine kinase 3 ligand (Flt3L). Combined delivery of these vectors elicits tumor cell death and an anti-tumor adaptive immune response that requires TLR2 activation. The implications of our studies indicate that the combined cytotoxic and immunotherapeutic strategies are effective strategies to combat deadly brain tumors and warrant their implementation in human Phase I clinical trials for GBM. © 2012 Elsevier Ireland Ltd.Fil: Assi, Hikmat. University of Michigan; Estados Unidos. David Geffen School of Medicine; Estados UnidosFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Baker, Gregory. University of Michigan; Estados Unidos. David Geffen School of Medicine; Estados UnidosFil: Mineharu, Yohei. David Geffen School of Medicine; Estados UnidosFil: Lowenstein, Pedro R.. University of Michigan; Estados UnidosFil: Castro, Maria Gabriela. University of Michigan; Estados UnidosElsevier Ireland2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67290Assi, Hikmat; Candolfi, Marianela; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro R.; et al.; Gene therapy for brain tumors: Basic developments and clinical implementation; Elsevier Ireland; Neuroscience Letters; 527; 2; 10-2012; 71-770304-3940CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0304394012010427info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neulet.2012.08.003info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:46:04Zoai:ri.conicet.gov.ar:11336/67290instacron: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:34982025-09-29 09:46:04.455CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Gene therapy for brain tumors: Basic developments and clinical implementation
title Gene therapy for brain tumors: Basic developments and clinical implementation
spellingShingle Gene therapy for brain tumors: Basic developments and clinical implementation
Assi, Hikmat
Cytotoxic
Flt3l
Gene Therapy
Glioblastoma
Immunotherapy
Tk
Viral Vectors
title_short Gene therapy for brain tumors: Basic developments and clinical implementation
title_full Gene therapy for brain tumors: Basic developments and clinical implementation
title_fullStr Gene therapy for brain tumors: Basic developments and clinical implementation
title_full_unstemmed Gene therapy for brain tumors: Basic developments and clinical implementation
title_sort Gene therapy for brain tumors: Basic developments and clinical implementation
dc.creator.none.fl_str_mv Assi, Hikmat
Candolfi, Marianela
Baker, Gregory
Mineharu, Yohei
Lowenstein, Pedro R.
Castro, Maria Gabriela
author Assi, Hikmat
author_facet Assi, Hikmat
Candolfi, Marianela
Baker, Gregory
Mineharu, Yohei
Lowenstein, Pedro R.
Castro, Maria Gabriela
author_role author
author2 Candolfi, Marianela
Baker, Gregory
Mineharu, Yohei
Lowenstein, Pedro R.
Castro, Maria Gabriela
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cytotoxic
Flt3l
Gene Therapy
Glioblastoma
Immunotherapy
Tk
Viral Vectors
topic Cytotoxic
Flt3l
Gene Therapy
Glioblastoma
Immunotherapy
Tk
Viral Vectors
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Glioblastoma multiforme (GBM) is the most common and deadliest of adult primary brain tumors. Due to its invasive nature and sensitive location, complete resection remains virtually impossible. The resistance of GBM against chemotherapy and radiotherapy necessitate the development of novel therapies. Gene therapy is proposed for the treatment of brain tumors and has demonstrated pre-clinical efficacy in animal models. Here we review the various experimental therapies that have been developed for GBM including both cytotoxic and immune stimulatory approaches. We also review the combined conditional cytotoxic immune stimulatory therapy that our lab has developed which is dependent on the adenovirus mediated expression of the conditional cytotoxic gene, Herpes Simplex Type 1 Thymidine Kinase (TK) and the powerful DC growth factor Fms-like tyrosine kinase 3 ligand (Flt3L). Combined delivery of these vectors elicits tumor cell death and an anti-tumor adaptive immune response that requires TLR2 activation. The implications of our studies indicate that the combined cytotoxic and immunotherapeutic strategies are effective strategies to combat deadly brain tumors and warrant their implementation in human Phase I clinical trials for GBM. © 2012 Elsevier Ireland Ltd.
Fil: Assi, Hikmat. University of Michigan; Estados Unidos. David Geffen School of Medicine; Estados Unidos
Fil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Baker, Gregory. University of Michigan; Estados Unidos. David Geffen School of Medicine; Estados Unidos
Fil: Mineharu, Yohei. David Geffen School of Medicine; Estados Unidos
Fil: Lowenstein, Pedro R.. University of Michigan; Estados Unidos
Fil: Castro, Maria Gabriela. University of Michigan; Estados Unidos
description Glioblastoma multiforme (GBM) is the most common and deadliest of adult primary brain tumors. Due to its invasive nature and sensitive location, complete resection remains virtually impossible. The resistance of GBM against chemotherapy and radiotherapy necessitate the development of novel therapies. Gene therapy is proposed for the treatment of brain tumors and has demonstrated pre-clinical efficacy in animal models. Here we review the various experimental therapies that have been developed for GBM including both cytotoxic and immune stimulatory approaches. We also review the combined conditional cytotoxic immune stimulatory therapy that our lab has developed which is dependent on the adenovirus mediated expression of the conditional cytotoxic gene, Herpes Simplex Type 1 Thymidine Kinase (TK) and the powerful DC growth factor Fms-like tyrosine kinase 3 ligand (Flt3L). Combined delivery of these vectors elicits tumor cell death and an anti-tumor adaptive immune response that requires TLR2 activation. The implications of our studies indicate that the combined cytotoxic and immunotherapeutic strategies are effective strategies to combat deadly brain tumors and warrant their implementation in human Phase I clinical trials for GBM. © 2012 Elsevier Ireland Ltd.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
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/11336/67290
Assi, Hikmat; Candolfi, Marianela; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro R.; et al.; Gene therapy for brain tumors: Basic developments and clinical implementation; Elsevier Ireland; Neuroscience Letters; 527; 2; 10-2012; 71-77
0304-3940
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67290
identifier_str_mv Assi, Hikmat; Candolfi, Marianela; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro R.; et al.; Gene therapy for brain tumors: Basic developments and clinical implementation; Elsevier Ireland; Neuroscience Letters; 527; 2; 10-2012; 71-77
0304-3940
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://linkinghub.elsevier.com/retrieve/pii/S0304394012010427
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neulet.2012.08.003
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
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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
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score 13.070432

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