title: A therapeutic cancer vaccine against GL261 murine glioma.
abstract: BACKGROUND
  Glioblastoma (GBM) is the deadliest of brain tumors. Standard treatment for GBM is surgery, followed by combined radiation therapy and chemotherapy. Current therapy prolongs survival but does not offer a cure. We report on a novel immunotherapy against GBM, tested in an animal model of C57BL/6 mice injected intra-cranially with a lethal dose of murine GL261 glioma cells.
  
  
  METHODS
  Ten week-old C57BL/6 mice were anesthetized before injection of 2 × 10(4) GL261 cells in the right cerebral hemisphere and after 3 days half of the mice were administered a single subcutaneous (s.c.) injection of irradiated semi-allogeneic vaccine, while mock-vaccinated mice received a s.c. injection of phosphate-buffered saline (PBS). Tumor engraftment was monitored through bioluminescence imaging (BLI). Length of animal survival was measured by Kaplan-Meier graphs and statistics. At time of sacrifice brain tissue was processed for estimation of tumor size and immunohistochemical studies.
  
  
  RESULTS
  Overall survival of vaccinated mice was significantly longer compared to mock-vaccinated mice. Five to ten percent of vaccinated mice survived more than 90 days following the engraftment of GL261 cells in the brain and appeared to be free of disease by BLI. Tumor volume in the brain of vaccinated mice was on average five to ten-fold smaller compared to mock-vaccinated mice. In vaccinated mice, conspicuous microglia infiltrates were observed in tumor tissue sections and activated microglia appeared to form a fence along the perimeter of the tumor cells. The results of these animal studies persuaded the Office of Orphan Products Development of the Food and Drug Administration (FDA) to grant Orphan Drug Designation for treatment of GBM with irradiated, semi-allogeneic vaccines.
  
  
  CONCLUSIONS
  Our preclinical observations suggest that semi-allogeneic vaccines could be tested clinically on subjects with GBM, as an adjuvant to standard treatment.
authors.affiliation: Department of Pharmaceutical Sciences, University of South Florida, Tampa, FL, 33612, USA. kindym@health.usf.edu.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kindy
authors.affiliation: Department of Pharmaceutical Sciences, University of South Florida, Tampa, FL, 33612, USA. jinyu@health.usf.edu.
authors.forename: Jin
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Sciences, University of South Florida, Tampa, FL, 33612, USA. hongzhu@health.usf.edu.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA. smithti@musc.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Smith
authors.affiliation: Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, 29425, USA. gattonis@musc.edu.|Ralph H. Johnson VA Medical Center, Charleston, SC, 29401, USA. gattonis@musc.edu.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Gattoni-Celli
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008163:Luminescent Measurements; D008297:Male; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D013194:Staining and Labeling; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D009195:Peroxidase