title: Current status of immunotherapy and gene therapy for high-grade gliomas.
abstract: BACKGROUND
  Despite improvements in surgical technique, radiation therapy delivery, and options for systemic cytotoxic therapy, the median survival for patients with newly diagnosed glioblastoma multiforme remains poor at 15 months with trimodality therapy. Multiple immunologic approaches are being tested to enhance the response of these tumors to existing therapy and/or to stimulate innate immune responses.
  
  
  METHODS
  We review the existing data that support the continued development of immunologic therapy in the treatment armamentarium against glioblastoma multiforme, with a focus on clinical data documenting outcomes.
  
  
  RESULTS
  In phase I and phase II trials, antitumor vaccines (dendritic and formalin-fixed) have demonstrated clinical efficacy with mild toxicity, suggesting that innate immune responses can be amplified and directed against these tumors. Suicide gene therapy (gene-mediated cytotoxic therapy) using a number of viral vectors and molecular pathways has also shown efficacy in completed phase I and ongoing phase II trials. In addition, neural stem cells are being investigated as vectors in this approach.
  
  
  CONCLUSIONS
  Although phase III data are needed before immunologic therapies can be widely implemented into clinical practice, the existing phase I and phase II data suggest that these therapies can produce meaningful and sometimes durable responses in patients with glioblastoma multiforme with mild toxicity compared with other existing therapies.
authors.affiliation: 21st Century Oncology Translational Research Consortium, Peoria, AZ 85381, USA. jmarsh@rtsx.com
authors.forename: James C
authors.initials: JC
authors.lastname: Marsh
authors.forename: Justin
authors.initials: J
authors.lastname: Goldfarb
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Shafman
authors.forename: Aidnag Z
authors.initials: AZ
authors.lastname: Diaz
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines