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UMD professor receives $375,000 grant to develop cancer vaccine technology

article7731.large_Alexandra “Alex” Scott was not even a year old when she was diagnosed with neuroblastoma, a common pediatric cancer that causes nerve cells to transform into tumors. Her parents were told that if she beat cancer, she would likely never walk again, that she would essentially be immobile. But that just wasn’t the case.

Alex moved her leg slightly just two weeks later and and right before her second birthday she was able to stand with the help of leg braces. Alex appeared to be that special patient all doctors hope for, the one that survives against all odds until it was discovered that her tumors had started growing again. It was then that Alex decided to take control.

After receiving a cell transplant she told her mother, “when I get out of the hospital I want to have a lemonade stand.” She said she wanted to give the money to doctors to allow them to “help other kids, like they helped me.” Alex followed through, too, raising an impressive $2,000 for “her hospital.”

Alex lost her battle with cancer in August of 2004, but her memory still lives on. She raised more than $1 million to help find a cure for her disease, firmly believing in the adage ‘when life gives you lemons, make lemonade.’

Now you’re probably wondering how this story has anything to do with University of Maryland assistant professor Christopher M. Jewell receiving a three-year $375,000 research grant for the pre-clinical development of a cancer vaccine technology he’s in the midst of creating. Well, turns out the funding he was awarded came from none other than the organization established in Alex’s memory, the Alex’s Lemonade Stand Foundation. Hopes are that with Jewell’s prototype vaccine, kids like Alex will have a chance at a better, healthier life.

Micahel HolahanThe vaccine works by using “a unique combination of nanotechnology and immunology to ‘raise an army’ of tumor-hunting immune cells, equip them to attack neuroblastoma, and leave them ready to reactivate if the cancer returns,” according to UMD Right Now.

Jewell’s goal is to enhance the immune system’s natural response to a threat, specifically neuroblastoma, by “encouraging T cells to multiply and become central memory T cells specific for tumor antigens.” T cells are a type of activated immune cell known for its ability to effectively infiltrate tumors.

He believes that by developing a biomaterials-based vaccine focused on using T cells to ward of neuroblastoma, oncologists will be able to have a treatment that works with a patient’s natural defenses rather than tear away at the body using traditional modes like radiation and chemotherapy.

What’s unique about this specific vaccine is that biodegradable polymer “depots” are injected right into the lymph nodes. This way the depots can protect the components of the vaccine and control when they’re released. Which is especially important for Jewell’s vaccine that not only contains the antigen that encourages T cells to attack neuroblastoma cells but also “immune signals,” which mimic the chemical signals immune cells use to correspond with one another.

“Cancer vaccines represent a new class of therapies, and biomaterials have great potential to treat cancers like neuroblastoma,” Jewell explained in a statement. “This investment will have a lasting impact on my lab’s ability to contribute to the pediatric cancer field.”

Jewell believes that this new technology could be used to treat other types of cancer as well, instilling a new sense of hope for families like Alex’s.

Image via UMD

Related story:

Homegrown’ research at GRU gets award grant of $375,000

By Tom Corwin, Staff Writer, the Augusta Chronicle

A “homegrown” researcher at Georgia Regents University Cancer Center is looking to make a pioneering discovery at Medical College of Georgia into a potential treatment for brain tumors in children. The work recently landed a three-year award from a leading foundation funding research into treatments for children with cancer.

PHOTO: MICHAEL HOLAHAN/STAFF

Alex’s Lemonade Stand Foundation awarded Dr. Ted Johnson the grant. Jay Scott, the foundation’s co-executive director, said he was chosen because he has kids first in mind.

Alex’s Lemonade Stand Foundation said it is giving an ‘A’ Award Grant of $375,000 over three years to Dr. Theodore Johnson at GRU Cancer Center, the first time the foundation has given an award to the school.

As part of the treatment for pediatric brain tumors, Johnson is looking to block an enzyme called indoleamine 2,3-dioxygenase or IDO as part of an immunotherapy that would increase the impact of chemotherapy and radiation therapy. IDO was first reported by GRU Cancer Center researchers Andrew Mellor and David Munn in 1998 as a mechanism that creates tolerance by a mother’s immune system for the developing fetus during pregnancy. It is in clinical trials in adults for lung cancer, ovarian cancer and metastatic breast cancer and melanoma.

“This one stood out from all of the ones that we received as being potentially impactful to kids with cancer,” said Jay Scott, co-executive director of the foundation. “One of the things we like to do with our grants is, could this project impact a kid with cancer within five years? If we can answer yes to this then we really like the projects even more.”

It is fitting that Johnson would be working with IDO: he did a summer rotation with Mellor in 1998 as he and Munn were putting together the first paper on it. Mellor was his doctoral adviser as he worked toward his MD/PhD degree from MCG in 2004, with IDO as the subject of his thesis. He considers himself “a homegrown entity.”

Having someone like that work on childhood cancer issues is what the foundation is about because too often cancer drugs are developed with adults in mind, Scott said.

“A lot of times we get the hand-me-down stuff, where it’s an afterthought,” he said. “We like things that think of kids first. This researcher is a pediatric oncologist so he has kids first in mind, which we really like.”

Drug development for childhood cancer is more difficult because there are much fewer cases to treat – it accounts for less than 1 percent of all cancers, an estimated 11,630 new cases in 2013 vs. 1.66 million new cases of cancer overall, according to the American Cancer Society. Drug companies don’t have the financial incentive to develop drugs in kids that would pay back the considerable research dollars needed to develop them, Johnson said. Thus having the support of the foundation is crucial for an early-stage researcher whose lab is just now getting promising results, Johnson said.

“For a foundation like Alex’s Lemonade Stand to fill the gap during a very lean period of federal funding is absolutely critical for labs like mine to even be open,” he said. “Frankly, without their funding, I don’t know that the lab would continue to be open. So we’re very thankful and very excited about this grant.”

Research like Johnson’s that seek to use the immune system to attack the tumor also hold greater promise of avoiding the toxicity that traditional approaches carry for kids, Scott said.

“Chemotherapies that work in adults have devastating effects on kids because of the way their bodies are growing,” he said. About 70 percent of childhood cancer survivors have some lifelong side effect from either the cancer or the treatment, Scott said.

“The first goal is to save the kid. The second is to have a great quality of life,” he said. “If you can have both of them together it’s an ideal world.”

Johnson’s research would still rely on traditional chemotherapy and radiation therapy to attack the brain tumors – in this case deadly glioblastoma multiforme – but blocking IDO would have an additive effect. Johnson was a co-author on Munn’s groundbreaking 2002 study that showed IDO was a mechanism by which tumors escape the host immune system.

Johnson thinks blocking IDO in the brain might have a different effect. With brain tumors, chemotherapy and radiation cause an inflammatory response that cause the immune system to recognize the tumor as foreign and attack it but with IDO active “the immune response is immediately quenched,” Johnson said. “Blocking IDO allows that immune response after (treatment) to continue, to get out of its early stages and evolve into a potent antitumor weapon. That’s what our data is showing and that’s what we hope we’ll see when we move this to the clinical trials.”

Those trials would be the first of their kind in kids and the hope would be to start them as early as two years from now, he said.

“My goal with our work in the lab is to teach the immune system that the tissue making up the brain tumor is not supposed to be there,” Johnson said. “The immune system itself has all the tools it needs to traffic anywhere in the body and create all of the damage that it needs to fight these tumors.”

For more on this story go to:

http://chronicle.augusta.com/news/health/2014-01-08/homegrown-research-gru-gets-award-grant-375000?v=1389223562

 

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