Gene therapy for brain tumors: Basic developments and clinical implementation

Authors
Assi, Hikmat; Candolfi, Marianela; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro R.; Castro, Maria Gabriela
Publication Year
2012
Language
English
Format
article
Status
Published version
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.
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
Subject
CYTOTOXIC
FLT3L
GENE THERAPY
GLIOBLASTOMA
IMMUNOTHERAPY
TK
VIRAL VECTORS
Otras Biotecnologías de la Salud
Biotecnología de la Salud
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/67290