When Mycah Clemons’ 4-year-old daughter died of a brain tumor in 2014, Clemons wanted to help others affected by the disease that took Mayianna’s life — a fast-growing cancer called diffuse intrinsic pontine glioma, or DIPG.
Clemons donated the tumor to the Stanford Medicine lab of Michelle Monje, MD, PhD, professor of neurology and neurological sciences, whom she had contacted months earlier for advice on her daughter’s case.
During that conversation, Monje had asked Clemons to consider providing the tumor for research. Monje’s team was the first in the world to culture donated tumors and study the cells directly.
“Talking to Dr. Monje, that’s when I learned that tumor donation was essential to finding out more about DIPG,” Clemons said.
DIPG tumors affect a few hundred children in the United States each year and have a grim prognosis, with a five-year survival rate below 1%. Yet Clemons had mixed feelings about donating the tumor: The idea that the aggressive tumor could continue to exist after Mayianna’s death disturbed her. “Especially with a child so young, it’s hard to process,” she said.
Clemons’ choice to donate was driven by a steadfast desire to enable scientific advances that might prevent families from losing a child the way she did.
She also led efforts to raise about $6,000 for Monje’s lab by hosting events such as a fashion show and a dance for friends and family in Pittsburgh and by selling DIPG awareness merchandise on a website she founded. Clemons, her family and her community are still raising funds to support the lab, hoping to reach a total of $30,000.
Since 2009, Monje’s team has received 87 DIPG tumor donations, allowing them to study the malignant cells in the lab and in animal models and to share DIPG cells with scientists around the world.
For each donated tumor, the scientists coax live cells from dead debris, culture the living cells in baths of liquid cell food, then put them to work for experiments. The research has revealed unique DIPG cell features that may be good cancer-treatment targets, which could be revolutionary for a disease that currently has no effective chemotherapy.
Clemons’ financial donation funded a summer scholarship that allowed an undergraduate student in Monje’s lab, Evan Arnold, to undertake a key project in 2016: He screened DIPG cells to see what molecules protruded from the cell membranes, showing that the cells abundantly display a molecular marker called GD2.
“It was a big surprise because it’s not a protein,” said Monje, noting that most research on brain cancer cells’ identifying markers has focused exclusively on proteins. GD2 is a ganglioside, made of two long fingers of fat that embed themselves in the cell membrane, anchoring a complex, lumpy sugar that sticks out from the cell.
If Arnold had used the other screening methods — such as looking at data from frozen tissue samples that indicates protein production — instead of studying living cells from donated tumors, the discovery would have been missed.
Gangliosides’ roles are just starting to be understood. The body normally uses GD2 judiciously, putting small amounts on certain nerves and brain cells as a “don’t eat me” signal to the immune system. But scientists have found much more GD2 on some cancer cells, which suggests it could be targeted for cancer treatment.
In fact, at the time of Arnold’s project, cancer immunotherapy expert Crystal Mackall, MD, professor of pediatrics and of medicine, had already engineered an anti-cancer immune cell known as a chimeric antigen receptor T cell, or CAR-T cell, to target GD2.
“We knocked on her door and said, ‘You have a CAR-T cell that targets this?’” Monje said. They teamed up and showed the cells could make DIPG tumors disappear in mice.
Now the team is testing the effects of anti-GD2 CAR-T cells on people with brain and spinal cord tumors. Though the trial’s first four patients eventually died of their disease, their experiences showed that it’s possible to reverse severe debilities caused by the tumors.
CAR-T cells helped the trial’s second patient, a young man named Jace Ward, temporarily regain an almost-normal gait and the ability to open his mouth after the tumor left him struggling to walk and eat.
“He went in in a wheelchair and walked out of the hospital,” said Jace’s mom, Lisa Ward, recalling her son’s treatment with CAR-T cells. “It was so freeing for him, such a good glimmer of hope.”
The discoveries that began with donations from Clemons and other bereaved families give Monje a lot of hope.
“Mycah worked for a year to come up with the funds for Evan’s project, and this is what it turned into,” Monje said. Clinical trials continue, with the scientists refining how the powerful immune cells can help patients.
“I’m really proud that they’re creating something all DIPG families want: the opportunity to have something promising when they reach out to a doctor,” said Clemons. “It’s bittersweet … but to see it happening is so exciting.”
Recalling how she felt when anti-GD2 cells first reversed Jace’s symptoms, Monje said, “I felt for the first time that we were going to be able to cure this disease someday.”