Canine Brain Tumor Research May Speed Human Trials

December 11, 2017

Dogs and humans share a particularly deadly form of brain cancer: glioblastoma. A new five-year canine cancer research project, awarded to the University of Minnesota, may improve survival rates in dogs and give researchers more insight into glioblastoma to apply to human trials. The $2.7 million grant funded as part of the 21st Century Cures Act by the National Cancer Institute, part of the National Institutes of Health, is led by Dr. Liz Pluhar, professor of veterinary surgery at the University of Minnesota College of Veterinary Medicine.

Glioblastomas are a highly invasive tumor that carries a grim prognosis in humans, with a median survival of 14 months despite surgery, radiation, and chemotherapy. Pet dogs diagnosed with these tumors have few treatment options and are often euthanized shortly after diagnosis. Pluhar’s project hopes to improve those outcomes by combining complementary therapies.

The study will use pet dogs with spontaneous tumors. It also renews a partnership between the U of MN’s veterinary college, the Masonic Cancer Center, and the University of Michigan Medical School. The group has worked together in the past, treating dogs with glioblastomas with gene-based immunotherapy.

The group had previously demonstrated a beneficial effect of vaccines made from each dog’s own tumor cells grown under special conditions and then killed. This “tumor lysate” is seen by the dog’s immune system as foreign, so the vaccine incites a specific immune response against the tumor cells.

In another earlier study, the team treated pet dogs with glioblastomas by using adenoviral-mediated gene therapy developed by the University of Michigan’s Dr. Maria Castro and Dr. Pedro Lowenstein. This treatment also prolonged progression-free times and overall survival with no adverse side effects.

Although both approaches were successful at prolonging survival for most patients, the tumor recurred over time. To improve the efficacy of both therapies, Dr. Michael R. Olin at the UMN discovered that the tumors secreted a substance that blocked the body’s natural immune response. He manufactured a peptide, CD200, which overrides the tumor’s efforts to protect itself from the body’s immune response.

The new research project hopes to demonstrate that the combination of immunotherapy with the added CD200 peptide in vaccines, and gene therapy in pet dogs with spontaneous high-grade gliomas is safe and effective. The team also hopes to learn more detailed information about the type of immune cells that kill tumor cells and delay disease progression or recurrence, as well as to assess whether there are molecular changes in tumor cells in response to immunotherapy.

Dr. Pluhar and collaborator, Dr. Matthew A. Hunt, are recruiting pet dogs with spontaneous glioblastomas as confirmed by MRI scans. They have funding to support treatment of at least 30 pet dogs, and will be performing all surgeries at the University of Minnesota.

To apply for the canine brain tumor clinical trials program visit: z.umn.edu/CanineBrainCancer

Funding information: National Institutes of Health (1U01CA224160-01) – Awarded to University of Minnesota. Principal Investigator, Liz Pluhar, DVM, PhD, University of Minnesota; Co- Investigators, Maria Castro, PhD, University of Michigan; Michael Olin, PhD, University of Minnesota; Pedro Lowenstein, MD, PhD, University of Michigan; Gerard O’Sullivan, PhD, University of Minnesota; Mathew Hunt, MD, University of Minnesota.