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National Brain Tumor Society Funding and Support of Innovative Research Helps Bring About an Immunotherapy Clinical Trial With Encouraging Results

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Today, encouraging results from a small, early-stage clinical trial for glioblastoma patients were reported in the scientific and medical journal, Clinical Cancer Research. The phase one study of 11 newly diagnosed glioblastoma (GBM) patients showed that combining an experimental immunotherapy with chemotherapy (temozolomide), along with an injection to prime the immune system, was well tolerated by patients, and also resulted in early signals of improved survival.

While the trial wasn’t designed (there was no control-arm) or powered (only 11 patients) to evaluate efficacy (success in improving survival), four of the patients receiving this combination did go on to survive for more than five years after treatment. Overall, the approach also showed signs of slowing the progression of patients’ tumors – where typically GBM tumors tend to begin to regrow after an average of approximately 8 months, study participants didn’t experience recurrence until a mean of 25 months.

The studies leaders have now received approval to launch a new trial to continue to evaluate this potential treatment.

“These are surprisingly promising clinical outcomes,” said the study’s senior author, Dr. John Sampson of Duke University. “However, it is important to emphasize that this was a very small study that used historical controls rather than randomizing patients to two different treatments, but the findings certainly support further study of this approach in larger, controlled clinical trials.”

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Dr. John Sampson at an NBTS event in 2013

The experimental vaccine at the heart of the trial was a dendritic cell vaccine that targets a specific protein in GBM cells that results from the presence of the cytomegalovirus (more below) in tumors. And, as the leaders of the new study note in a corresponding press release, this study is, “one in a sequence of clinical trials we have conducted to explore the use of an immunotherapy that specifically targets a protein on glioblastoma tumors.” They note, specifically, that this study built on earlier trials that found that this vaccine could be enhanced by first priming the immune system (work NBTS contributed funding to) and a separate study discovered that higher-than-standard doses of chemotherapy can also help enhance the impact of other vaccines in GBM (work NBTS also contributed to, separately).

Yet, beyond the immune stimulating techniques that the researchers used in their current study, NBTS has played a significant role in fostering the intriguing scientific history and journey of the cytomegalovirus as it relates to gliomas.

Shortly after the turn of the 21st century, Dr. Charles Cobb – at that time a physician and researcher at the University of Alabama, Birmingham – discovered that an indolent virus known as the cytomegalovirus (CMV) could be found in a large percentage (roughly 90-95%) of all glioblastoma tumors, but not healthy brain tissue.

At the time, Dr. Cobb hadn’t quite yet understood the full implications of what this discovery meant. But he had a hunch it was significant. Thus, in 2002 NBTS provided a grant for Dr. Cobb to study CMV further. Dr. Cobb was originally interested in understanding if the CMV is what was actually leading to the development of these tumors. While the jury is still out on that hypothesis, others in the field picked-up on Dr. Cobb’s discovery and began exploring if the presence of CMV in GBMs could actually be leveraged for therapeutic approach.

One of these researchers was Dr. Duane Mitchell, at the time at Duke University. Dr. Mitchell thought that it might be possible to use the presence of the virus within the tumor to elicit a response for the body’s own immune system to turn on the tumor and destroy it. Usually cancerous tumors are able to ‘hide’ themselves from the cells of the immune systems that would otherwise identify them as invaders. Thus, in 2004-2005, NBTS funded Dr. Mitchell to study if CMV could be targeted with a vaccine – like doctors do for long-defeated diseases like mumps, measles, and polio – that would reveal the CMV-infected tumor to immune cells.

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Dr. Duane Mitchell at an NBTS event in 2013

Dr. Mitchell’s work with his colleagues at Duke, including Dr. Sampson, began to indicate a real possibility for this treatment approach, and NBTS provided another round of funding to Dr. Mitchell in 2007. This work, in Dr. Mitchell’s words, “opened a new line of therapy directed at targeting CMV in malignant gliomas.”

Meanwhile, in 2009 NBTS hosted a seminal workshop with leaders from across not just the neuro-oncology field, but also virologists, to discuss CMV’s potential role in GBM.

Eventually, Mitchell’s data would validate Dr. Cobb’s initial findings, along with other independent studies from institutes in Sweden and at MD Anderson Cancer Center, including a couple of small, initial studies using CMV-vaccines to treat glioma patients. All of this work, built the foundation for, and aided, the advances which ultimately enabled progress to continue to the encouraging results from the clinical trial published today.

This is consistent with a number of additional investigational medicines in clinical trials that were seeded by funding support from NBTS, and other organizations that have embraced such ‘out-of-the-box’ thinking. Some of these other potential new treatments now under evaluation in clinical trials whose progress NBTS contributed to, include clinical trials of Toca 511 & Toca FC, a gene therapy approach, which just received “Breakthrough Therapy Designation” for treating high-grade gliomas; the poliovirus treatment, PVS-RIPO, also developed at Duke, which received “Breakthrough Therapy Designation” last year; the oncolytic adenovirus treatment DNX-2401 (formerly known as Delta-24), which was discovered with the help of NBTS grants to Dr. Juan Fueyo at MD Anderson Cancer Center, and is now in phase II clinical trial for glioblastoma.

As with all experimental treatments still going through the clinical trial process, early successes of any of the therapies noted above does not ultimately guarantee success in larger, more rigorous later-stage clinical trials. That said, it is heartening to see the fruits of years of scientific efforts begin to advance to the clinic, and the more research that can be translated into investigational medicines the greater the odds are that one or more of these cutting-edge therapies becomes the next tool in the growing toolbox neuro-oncologists have to treat this difficult disease.


To see a full list of clinical trials currently in pivotal, Phase III clinical trials, visit here.

To search for trials that may be right for you or your loved one, visit trials.braintumor.org.

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