title: Stem cell based glioblastoma gene therapy.
abstract: There is no curative therapy for glioblastoma multiforme (GBM) thus far. Combined therapies including surgery, followed by concomitant irradiation and chemotherapy with the DNA alkylating agent temozolomide (TMZ), slightly improves patients' survival but the prognosis remains poor. The fatal nature of glioblastoma is caused by tumor-initiating glioblastoma cells. The tumor tropic ability of adult mesenchymal stem cells offers the attractive possibility to use these cells as a vehicle to deliver therapeutic agents to the site of the tumor. In preclinical studies using animal models, mesenchymal stem cells engineered to express suicide genes were shown to elicit a significant antitumor response against various tumors including glioblastoma. This review summarizes the current state of knowledge about stem cell directed glioblastoma therapy. Results obtained in a preclinical study using mesenchymal stem cells engineered to express cytosine deaminase provided evidence that stem cell based gene therapy might also attack glioblastoma stem cells and therefore be curative. In addition to stem cell directed prodrug gene therapies, other immunotherapeutic modalities using mesenchymal stem cells are discussed as well. Encouraging results of preclinical studies of stem cell based gene therapy for glioblastoma support the argument to begin clinical studies.
authors.affiliation: Cancer Research Institute SAS, Bratislava, Slovakia. exonalt@savba.sk
authors.forename: C
authors.initials: C
authors.lastname: Altaner
authors.forename: V
authors.initials: V
authors.lastname: Altanerova
mesh_terms: D000818:Animals; D043525:Cytosine Deaminase / Q000235:genetics; D005437:Flucytosine / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics
chemical_list: D005437:Flucytosine; D013937:Thymidine Kinase; D043525:Cytosine Deaminase; D015774:Ganciclovir