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.
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.”