DIPG Dialogue

Just One More Day is starting a new regular blog feature called DIPG Dialogue which will contain interviews with researchers, physicians and other advocates in the DIPG community.

Introduction:

Dr. Ohlfest is an Assistant Professor and the Director of the gene therapy program in Department of Neurosurgery and a faculty member of the Stem Cell Institute. Dr. Ohlfest studied molecular biology as an undergraduate at Iowa State University and received his Ph.D. in molecular genetics and cell biology at the University of Minnesota. He then did post-doctoral research with Dr. Andrew Freese at the University of Minnesota focusing on gene therapy in the central nervous system. Dr. Ohlfest's research interests are focused on using gene transfer to correct disease and manipulating endogenous progenitor cells by gene transfer. In addition, targeted therapies for the eradication of so called "brain tumor stem cells", the tumor cells capable of self-renewal and the cause of tumor relapse, is an area of ongoing investigation in his lab.


Questions & Answers:

Dr Ohlfest, it seems that you have a super hero, Batman, that just might be making a difference for children with brain tumors. How is that?

Batman was the first dog to undergo an experimental treatment for glioma, an aggressive form of brain cancer. Batman was treated with the combination of surgery, gene therapy, and anti-tumor vaccination in the summer of 2008. Remarkably, Batman is alive and tumor-free nearly one year later. This novel treatment could only be tested in a large animal because mice, the standard preclinical "model" for testing new therapy, are just too small. Specifically, the brains of mice are not amenable to surgery where the gene therapy can be deposited into the resection site to hit the tumor cells left behind. In dogs we can use the same dose of gene therapy and vaccine that would be given to people. Because of this, we not only help the dog, we also get answers about effectiveness and safety that can be extrapolated to human patients.

We feel the treatment of dogs can revolutionize the way clinical trials are done for brain tumor patients. By using the dog data to justify dose, timing, and drug choices, it may become possible to test several experimental agents in a single phase I trial, a scenario that seldom happens in modern neuro-oncology. This is important because history has shown that combination therapy is better than mono therapy, yet for brain tumor patients, most phase I clinical trial are restricted to single experimental drugs.


How does this type of treatment differ from other forms of treatment?

It does not involve chemotherapy or radiation, which those people familiar with DIPG know causes toxicity. Instead, we attempt to get the body to take care of the problem by activating a tumor-specific immune response. The vaccine and gene therapy we are using have been optimized for potency over the last 4 years. They are superior to some of the first generation vaccines and gene therapies that were developed in the 1990s and first part of this decade.


What have the results been so far with the dogs?

We have documented stable disease, and tumor regressions, with minimal side effects. Four dogs have been treated to date, although we are going to enroll dozens more.


It seems that this approach is something that you feel strongly about, why is that?

I have seen first hand what brain cancer and brain cancer therapy does to people. My grandmother died from therapy-induced toxicity after her ovarian cancer spread into her brain. She was participating in a clinical trial where chemotherapy was directly administered into the brain. At that time, I thought “we can do better” and I still believe that today. I think we have pushed radiation and chemotherapy to the upper limit. Fresh ideas are long over due. There is mounting evidence that the immune response controls cancer in many people spontaneously. We just need to learn how to direct the immune response to the right target.


Do you feel that this is something that truly can be translated to children- and specifically children with DIPGs? If so, how long would it take to get such a trial open?

Absolutely. DIPG is an ideal target for vaccine therapy in particular. In many cases, after radiation there is a large reduction in tumor burden, a perfect time to harness the immune response to target those few tumor cells that are left behind. A trial for DIPG using immunotherapy could be open in a year or less. That’s the best case. The rate limiting steps to getting this trial open are time (required to go through the process of FDA approval) and funding (to pay all costs associated with vaccine production and immune monitoring).


What sort of funding are you in need of?

Because DIPG is very rare, it can be difficult to get funding from the usual sources to focus on this particular tumor. We are in need of funding to conduct preclinical research focused on DIPG experimental therapeutics specifically. Additionally, funding is needed to support the first phase I clinical trial.


Besides raising money, is there anything that DIPG parents can do to help with your research?

Yes, spread the word. Learn more about our research by visiting www.braintumorlab.com and tell your friends.

Any dog with a brain tumor is eligible for consideration in one of our canine clinical trials. Most dog owners don’t know we are offering to pay for the entire cost of their dog’s therapy. We are treating these dogs with the intent to cure; this is not research for research’s sake.

In addition, tell your congressman and senators about the lack of funding for brain tumor research, and DIPG in particular. Less than 20% of grants submitted to the National Institutes of Health are funded. The state of Minnesota could develop a brain cancer research bill, similar to California (stem cells) or Texas (cancer research). We can do better, but it will require a change in priorities at the state and federal level.

To see a video clip featuring Batman and Dr. Ohlfest, click here: