Anti-tumor immune response correlates with neurological symptoms in a dog with spontaneous astrocytoma treated by gene and vaccine therapy

Liz Pluhar, Patrick T. Grogan, Charlie Seiler, Michelle Goulart, Karen S. SantaCruz, Cathy S Carlson, Wei Chen, Michael R Olin, Pedro R. Lowenstein, Maria G. Castro, Stephen J Haines, John R. Ohlfest

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 (IFNγ) gene transfer, and vaccination with glioma cell lysates mixed with CpG oligodeoxynucleotides. Surgical tumor debulking and delivery of Ad-IFNγ 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.

Original languageEnglish (US)
Pages (from-to)3371-3378
Number of pages8
JournalVaccine
Volume28
Issue number19
DOIs
StatePublished - Apr 26 2010

Bibliographical note

Funding Information:
This work was supported by grants from the National Institutes of Health/National Institute of Neurological Disorders & Stroke (NIH/NINDS) NIH IR21-NS055738 (JRO), American Cancer Society RSG-09-189-01-LIB (JRO), Randy Shaver Cancer Research and Community Fund (JRO), Children's Cancer Research fund (JRO and GEP). MGC's and PRL's research program on brain tumor biology and therapeutics is supported by NIH/NINDS Grant 1UO1 NS052465; 1RO1-NS 057711; 1R21-NSO54143; 1 RO1 NS 054193; RO1 NS 42893. The Bram and Elaine Goldsmith and the Medallions Group Endowed Chairs in Gene Therapeutics to PRL and MGC, respectively. The Drown Foundation; The Linda Tallen & David Paul Kane Foundation and the Board of Governors at CSMC. The authors thank the Chunyan Liu at Cedars Sinai Medical Center/UCLA for the preparation of the Ad-IFN and the Comparative Pathology Shared Resource of the University of Minnesota Masonic Cancer Center for preparation of the histological sections.

Keywords

  • Adenovirus
  • Canine glioma
  • CpG ODN
  • Gemistoctyic astrocytoma
  • Interferon gamma

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