• Vibrant, kind-hearted, and articulate little Maiyanna was only 4 years old when she passed away on April 16, 2014, from diffuse intrinsic pontine glioma (DIPG), a rare and inoperable brain tumor.
  • Michelle Monje, MD, PhD, (right) explains the life-saving research happening in her lab to Mycah Clemons, who donated her daughter's tumor to research.
  • With funding from Maiy's Miracle, Evan Arnold (right) conducted the first of a series of experiments that have led to a possible treatment for DIPG.
  • "It's important for me to fundraise to help other families so the next family who calls Dr. Monje looking for help will get a voice of excitement and reassurance that she can offer something promising for their child and family," says Mycah Clemons.
 

 

One Step Closer to a Cure

Jennifer Yuan
Monday, May 21, 2018

Vibrant, kind-hearted, and articulate little Maiyanna was only 4 years old when she passed away on April 16, 2014, from diffuse intrinsic pontine glioma (DIPG), a rare and inoperable brain tumor. On April 16, 2018, the fourth anniversary of her passing, something incredible happened.

When Maiy died, her mom, Mycah Clemons, was determined to honor her and prevent other families from suffering the same loss. Not only did she donate her daughter’s tumor to science, she also raised funds from her community in Pittsburgh, Pa., to support groundbreaking research at Stanford with hopes of finding a cure. 

This spring, a surprisingly successful study, kickstarted by funding from Maiy’s family and friends, was published in Nature Medicine. 

A press release issued on April 16 from the School of Medicine shared the exciting news:

Engineered human immune cells can vanquish a deadly pediatric brain tumor in a mouse model, a study from the Stanford University School of Medicine has demonstrated. 

The study represents the first time diffuse intrinsic pontine glioma has been eradicated in mice. DIPG affects a few hundred school-age children across the country each year and has a median survival time of only 10 months; there is no cure. In mice whose brainstems were implanted with human DIPG, engineered immune cells known as chimeric antigen receptor T cells—or CAR-T cells—were able to eliminate tumors, leaving very few residual cancer cells.

We spoke with Mycah and senior author Michelle Monje, MD, PhD, assistant professor of neurology and the Anne T. and Robert M. Bass Endowed Faculty Scholar, to hear more about how this remarkable discovery came about—and why your support is so essential to pediatric research. 

What inspired you to support DIPG research at Stanford? 

MYCAH: Maiyanna had only been on this earth for three years before Children’s Hospital Pittsburgh discovered a massive DIPG tumor on her brainstem in May 2013. We started doing our research and found that Dr. Michelle Monje at Lucile Packard Children’s Hospital Stanford was the leading DIPG researcher in the world. 

When I called Dr. Monje looking for help, this apologetic and empathetic voice on the other end of the phone told me unfortunately there is nothing promising in terms of treatment she could offer.

Maiy never cried about her illness, even when she lost her ability to walk and play with friends and family. We kept busy enjoying organic foods, entering beauty pageants, traveling to Disneyland, having parties, painting our nails, and being princesses. 

When I finally accepted the reality that Maiy would die, I called Dr. Monje again to ask her about the process of tumor donation. I hadn’t yet filed the paperwork when Maiy passed away on the evening of April 16, 2014, at the age of 4. I called our local doctors to arrange for Maiy’s tumor donation, and surprisingly they told me they couldn’t get it done. So I called Dr. Monje’s office, and she got back to me right away, making sure that Maiy’s tumor was extracted. 

To this day, I am humbled by her hard work and ability to make the impossible possible. 

Your fundraiser, Maiy’s Miracle, raised $6,000. What did you hope to achieve? 

MYCAH: Maiy’s Miracle originated to give Maiy the best quality of life through her DIPG journey— to enjoy experiences with anyone who wanted to create special memories with her. After she passed away, we held a barbeque, paint party, and a butterfly release to celebrate her life and to raise awareness for DIPG. 

It’s important for me to fundraise to help other families so the next family who calls Dr. Monje looking for help will get a voice of excitement and reassurance that she can offer something promising for their child and family. 

Why is philanthropic support so essential to pediatric research? 

DR. MONJE: Even small gifts applied at important leverage points can make a big difference. Philanthropy is more important than ever for pushing the ball down the field for research, particularly for pediatric diseases. Donor support allows us to be very nimble and have funding already in place to follow up on new ideas, whereas government research grants might take six to 12 months to secure, if at all. 

What did you discover, and why is it so remarkable? 

DR. MONJE: With the funding from Maiy’s Miracle, we awarded a summer research scholarship to a Stanford undergraduate student to screen human DIPG tumor cultures for surface molecules that could act as targets for CAR-T cells. That started us down a path of discovery toward a new approach for eliminating DIPG. 

The press release goes on to share: 

The team identified a sugar molecule, GD2, which is abundant on the surface of DIPG tumors in 80 percent of cases. Scientists have known for decades that GD2 levels on some other forms of cancer are very high, but its discovery on this tumor came as a surprise, said Crystal Mackall, MD, professor of pediatrics and of medicine and the study’s other senior author, adding, “It was hiding in plain sight, and we didn’t know.”

Mackall, an expert in cancer immunotherapy, and her team had already designed a way to make CAR-T cells that attack the GD2 sugar [in other types of cancer]. Next, the team tested the GD2 CAR-T cells in mice whose brainstem was implanted with human DIPG tumors, an experimental system that Monje’s lab pioneered. 

In mice that received one intravenous injection of GD2 CAR-T cells, the DIPG tumors were undetectable after 14 days. 

DR. MONJE: I was pleasantly surprised with how well this worked. We gave CAR-T cells intravenously, and they tracked to the brain and cleared the tumor. It was a dramatically more marked response than I would have anticipated. 

What role did donor support play in this particular study? 

DR. MONJE: While the science and clinical possibilities are exciting, I was also struck by the collaboration and funding at key moments that made this come together. First we had funding from Maiy’s family to try out a new approach. Just as we were starting to see promise, Dr. Mackall reached out to me, and we recognized an opportunity to apply cancer immunotherapy to DIPG, which had never been done successfully before. The initial results were astounding, but we needed to replicate it. Right at that critical juncture, another foundation called Unravel Pediatric Cancer, started by another family who also sadly lost their child to DIPG, approached us with additional funding that allowed us to further test this risky approach. 

It felt like this project was meant to be. The timing was uncanny. 

The initial experiments, which we did not know would be so successful, would not have happened without Maiy’s family. And it was further expedited by Unravel Pediatric Cancer and other funders. 

So many donors, foundations, and families have supported DIPG research; many families have even made the unthinkable gift of donating their child’s brain tumor. 

They have all helped to expedite our work. Every single contribution, large or small, enables us to move forward without delay and do all we can to help families fighting this terrible disease. 

What does it mean to you to know that Maiy’s Miracle made this discovery possible? 

MYCAH: My prayers to Jehovah have been answered. It eases the grief knowing that my daughter’s journey was not in vain. My heartfelt prayer is that our efforts in donating Maiyanna’s tumor and supporting DIPG research at the Monje Lab make a difference so that families in the future could have hope when receiving a DIPG diagnosis. 

It’s astonishing how Maiy continues to inspire and make a difference to others. Progress in DIPG treatment truly means the world to us. This could be the miracle that all DIPG families pray for. 

Proceeding with caution: The team plans to move the CAR-T treatment into human clinical trials, but Monje cautions that the treatment, while promising, is also extremely risky. The location of the DIPG brain tumor and the inflammation caused by the therapy’s immune response both pose significant challenges. The team will build as many safeguards as possible into the trial to minimize risks to people who participate, Monje says.

Did you know?

When you give to the Children’s Fund, 33 cents of every dollar go to the Child Health Research Institute to support groundbreaking research.

This research was supported by a Stand Up To Cancer— St. Baldrick’s—National Cancer Institute grant. The research was also supported by the National Institute of Neurological Disorders and Stroke (grants F31NS098554 and R01NS092597); Abbie’s Army Foundation; Unravel Pediatric Cancer; Maiy’s Miracle Foundation; the McKenna Claire Foundation; Alex’s Lemonade Stand Foundation; Izzy’s Infantry Foundation; The Cure Starts Now Foundation and DIPG Collaborative; the Lyla Nsouli Foundation; Declan Gloster Memorial Funds; the N8 Foundation; Fly a Kite Foundation; the Liwei Wang Research Fund; the Virginia and D.K. Ludwig Fund for Cancer Research; the Sam Jeffers Foundation; the Reller Family Research Fund; the Child Health Research Institute at Stanford and SPARK program; and the Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases. Stanford’s departments of Neurology, of Pediatrics, and of Medicine also supported the work. 

Press release written by Erin Digitale and reprinted with permission from the School of Medicine’s Office of Communication & Public Affairs. The full release is available at med.stanford.edu/news.

This article originally appeared in the Spring 2018 issue of Packard Children’s News.

Photography credit: Mycah Clemons, Douglas Peck

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