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Feature

A close-up of the tumor removed from Batman, the dog

On August 5, U surgeons removed a brain tumor from a 10-year-old shepherd-mix named Batman. Gene therapy followed to mark the cancer cells and in several weeks, Batman will be injected with a vaccine containing tumor-specific immune cells that will migrate into the brain to kill the remaining cancer cells.

Exploring a new cancer therapy

Results of a two-part therapy may further treatment for people and other animals with brain tumors

August 12, 2008

In late July, a 10-year-old shepherd-mix dog named Batman (for his black, pointed ears that resemble the superhero) was diagnosed with a cancerous brain tumor that, left untreated, would have been fatal. With the permission of Batman's owners, researchers at the University of Minnesota successfully performed the first step of an experimental procedure to treat his cancer.

The three-hour surgery on August 5 involved removal of as much of the brain tumor as possible, followed by the injection of a gene therapy around the perimeter of the tumor area. The injection served to prime the remaining cancer cells for receiving a vaccine, which will be developed in the laboratory using tumor tissue removed during surgery. In several weeks, Batman will be injected with the vaccine.

To date, research has involved separate investigations of the impact of gene therapy and vaccines on brain tumors. The University of Minnesota scientists and clinicians conducting this research think that surgery followed by combining the two experimental agents in one study--a one-two punch of gene therapy followed by vaccine--may have a greater effect on the cancer. If this two-step process works, it could have a significant impact on improving treatment for brain tumors in animals and people.

"The problem with brain tumors is that they can hide from the immune system because the cancer cells typically don't have surface proteins that allow the immune system to recognize and kill them," Ohlfest says.

The procedure team included Elizabeth Pluhar, veterinary neurosurgeon and orthopedic surgeon; John Ohlfest, who directs the University's translational neurosurgery gene therapy program; and Stephen Haines, a neurosurgeon at the University of Minnesota Medical Center, Fairview.

The gene therapy used was a modified virus that cannot replicate and expresses the protein interferon gamma (IFN-g). IFN-g primed the tumor site, making the tumor cells more visible to Batman's immune system.

"The problem with brain tumors is that they can hide from the immune system because the cancer cells typically don't have surface proteins that allow the immune system to recognize and kill them," Ohlfest says. "IFN-g should reverse this, exposing the tumor to the immune system and allowing the vaccine to work at peak efficiency."

The tumor cells taken during the surgery will be killed in the laboratory to make one part of the vaccine. The other part of the vaccine will be an immunogenic--meaning able to produce an immune response--portion of DNA derived from bacterial DNA called CpG ODN.

"The CpG ODN serves to trick the dog's immune system into thinking it has a bacterial infection, only we will co-inject tumor cell proteins along with the CpG ODN so the immune system goes after the tumor [with a vigor similar to that with which it would go against bacteria]," Ohlfest said. "We expect that tumor-specific immune cells will then migrate into the brain to kill the remaining cancer cells."