title: Anti-tumor immune response correlates with neurological symptoms in a dog with spontaneous astrocytoma treated by gene and vaccine therapy.
abstract: Gene therapy and vaccination have been tested in malignant glioma patients with modest, albeit encouraging results. The combination of these therapies has demonstrated synergistic efficacy in murine models but has not been reported in large animals. Gemistocytic astrocytoma (GemA) is a low-grade glioma that typically progresses to lethal malignancy despite conventional therapies. Until now there has been no useful animal model of GemA. Here we report the treatment of a dog with spontaneous GemA using the combination of surgery, intracavitary adenoviral interferon gamma (IFNgamma) gene transfer, and vaccination with glioma cell lysates mixed with CpG oligodeoxynucleotides. Surgical tumor debulking and delivery of Ad-IFNgamma into the resection cavity were performed. Autologous tumor cells grew slowly in culture, necessitating vaccination with allogeneic tumor lysate in four of the five vaccinations. Transient left-sided blindness and hemiparesis occurred following the fourth and fifth vaccinations. These neurological symptoms correlated with a peak in the levels of tumor-reactive IgG and CD8(+) T cells measured in the blood. All symptoms resolved and this dog remains tumor-free over 450 days following surgery. This case report preliminarily demonstrates the feasibility of treating dogs with spontaneous glioma using immune-based therapy and warrants further study using this therapeutic approach.
authors.affiliation: Department of Veterinary Animal Clinical Sciences, University of Minnesota, St. Paul, MN 55108, United States.
authors.forename: G Elizabeth
authors.initials: GE
authors.lastname: Pluhar
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Grogan
authors.forename: Charlie
authors.initials: C
authors.lastname: Seiler
authors.forename: Michelle
authors.initials: M
authors.lastname: Goulart
authors.forename: Karen S
authors.initials: KS
authors.lastname: Santacruz
authors.forename: Cathy
authors.initials: C
authors.lastname: Carlson
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Mike R
authors.initials: MR
authors.lastname: Olin
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Lowenstein
authors.forename: Maria G
authors.initials: MG
authors.lastname: Castro
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Haines
authors.forename: John R
authors.initials: JR
authors.lastname: Ohlfest
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood*; D001254:Astrocytoma / Q000276:immunology / Q000601:surgery / Q000628:therapy / Q000662:veterinary*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002457:Cell Extracts / Q000008:administration & dosage / Q000276:immunology; D004283:Dog Diseases / Q000276:immunology* / Q000601:surgery / Q000628:therapy*; D004285:Dogs; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016233:Immunotherapy, Active / Q000379:methods*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; C408982:CPG-oligonucleotide; D002457:Cell Extracts; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma