As a child, Dylan Burke was an athlete and gymnast who shunned sugar and worked out every day, and a budding mad scientist who was constantly inventing things. As a patient, he grew interested in neuropharmacology and the chemical basis for happiness, reading journal papers together with his father.
Dylan was diagnosed at age 9 with myelodysplastic syndrome (MDS), a group of diseases characterized by abnormal production of blood cells in bone marrow. MDS commonly progresses to leukemia, and that was sadly Dylan’s experience. He came to Fred Hutch Cancer Center in 2019 for treatment after his father, Dave Burke, read a pediatric oncology textbook that included a chapter on MDS written by Soheil Meshinchi, MD, PhD, a hematologist/oncologist and professor in the Translational Science and Therapeutics Division at Fred Hutch and a member of its Immunotherapy Integrated Research Center.
“Soheil was largely the reason we chose Fred Hutch and Seattle Children’s Hospital,” said Burke, a Google advisor and chief technology officer at the Arc Institute, a biomedical research organization in Palo Alto, Calif. “He’s a really creative scientist and clinician who thinks outside the box and is disruptive and makes things happen. He is persistent. I have seen him fight not just for Dylan but for other children.”
Meshinchi, a world leader in developing novel approaches to treating acute myeloid leukemia (AML), has been named the second recipient of the Dylan Burke Endowed Chair in Immunotherapy. Fred Hutch immunologist Stan Riddell, MD, served at the inaugural holder of the chair, which Burke and his wife, Louise O’Reilly, established in 2020.
Dylan received a bone marrow transplant at Fred Hutch and was in remission for nearly two years when he relapsed. His cancer had acquired new mutations, which required new treatments. Dylan’s medical team performed molecular analyses of his cancer, searching for changes in genes or specific proteins to help create a targeted treatment plan for Dylan. With Meshinchi’s support, Dylan’s family pursued several drugs that had not yet been used in pediatric patients, including one that targeted the TP53 mutation that defined Dylan’s disease.
Dylan underwent a second transplant. When that didn’t control the cancer, Dylan’s parents tried other options including working with a start-up lab to design an assay, or test, that would yield a personalized chemotherapy plan. None of the approaches managed to contain the cancer, and Dylan died on June 26, 2022.
“Dylan never wanted to give up, and Soheil was an awesome partner,” said Burke. “Pediatric oncology as a vocation is incredibly tough. Soheil works so hard to push the science forward to help these kids.”
He and O’Reilly decided to endow the chair when Dylan was in remission.
“We wanted to give back a little,” he said. “I’m a big believer in harnessing the body’s immune system to fight cancer. Our goal is to accelerate the research that enhances this natural defense.”
Meshinchi’s lab focuses on researching the genetics of AML, the deadliest pediatric and adult leukemia. They have sequenced specimens from the largest cohort of AML cases in children and adults and maintain a biobank that stores more than 100,000 specimens from more than 3,000 patients — the largest of its kind anywhere.
In the past decade, the lab has advanced multiple novel targets from the discovery stage to clinical trials, including FOLR1, a gene that codes for folic acid receptor alpha protein, which is expressed in a highly lethal form of infant leukemia. A first-in-humans trial with FOLR1 immunotherapy, a form of CAR T-cell therapy, has been activated at Fred Hutch for treatment of infants. Additional newly developed CAR T-cell therapies are advancing into clinical trials in pediatric and adult AML.
Based on his observation that the FOLR1 protein is also expressed in osteosarcoma, an aggressive bone cancer, Meshinchi has launched a second FOLR1 CAR T-cell clinical trial for osteosarcoma in children and adults. Solid tumor cancers are a new area of focus for him.
Soheil Meshinchi’s work is also supported by Project Stella, named after Stella Novotny, who was just 4 years old when she died from AML. Like Dylan, Stella’s family relocated to Seattle to be treated by Meshinchi.
She was the only person enrolled in a first-in-humans clinical trial of an immunotherapy drug that homed in on a protein called PRAME that was expressed by her leukemia cells. That intitial dose wasn't strong enough to counteract Stella's disease, but Meshinchi's lab has since developed a more robust strain.
To honor Stella, her family created Project Stella, a philanthropic initiative at Fred Hutch that has raised more than $2.7 million to help develop and advance to the clinic a first-in-humans CAR T-cell therapy. An associated clinical trial is active and has enrolled five patients, demonstrating safety and efficacy.
"Soheil’s passion and dedication to understanding rare pediatric leukemias and delivering novel therapies is unparalleled,” said Carryn McLaughlin, a close family friend who leads fundraising efforts on behalf of the Novotnys.
“He is relentless, and Project Stella has benefited from his passion,” she said. “Soheil knows we are at the tip of the iceberg in terms of understanding the nuances of rare pediatric leukemias. He’s committed to delivering unique therapies to these kids because treatment in these situations is not one size fits all.”
Burke and his 8-year-old son, Zach — the youngest of Dylan’s three siblings — recently came to Fred Hutch from the Bay Area to congratulate Meshinchi in person and tour his lab, including the biobank, a massive cylindrical freezer. When Meshinchi opened the lid, liquid nitrogen vapor swirled out in a haze that resembled a scene from “Back to the Future.”
Dylan’s cells are in that freezer along with cells from many other children, allowing Meshinchi ’s lab to explore the efficacy of novel drug targets for AML thanks to specimen donations from families who want to pay it forward and help others with the disease.
On his trip to Seattle, Zach brought along Zaby, his AI teddy bear. Just like his big brother Dylan, Zach is constantly coming up with new inventions and enlisted his dad, Dave, to bring Zaby to life as a modified storytime bear with a powerful AI agent running in the bear’s backpack. Perched on a table in Meshinchi's office, Zaby was surprisingly well educated about the future of immunotherapy at Fred Hutch, explaining that Fred Hutch researchers such as Meshinchi are reprogramming T cells to fight cancer, which is like "teaching tiny soldiers to go and zap the bad cancer cells. One of the things they are working on is making these treatments work for solid tumors, not just blood cancers.”
In addition to developing AML therapies, Meshinchi’s lab is expanding research into solid cancers in adults including pancreatic cancer, uterine cancer and ovarian cancer, as well as pediatric brain tumors.
“Targets expressed in AML that we have discovered therapies for are also expressed in those malignancies,” said Meshinchi.
Meshinchi has also created an international collaboration with professor Franco Locatelli in Rome to activate his lab’s clinical trials in European countries.
“Therapies created here will be manufactured there and distributed to patients in Europe,” he said.
Meshinchi, who trained as a basic scientist, received his PhD in protein chemistry at the University of Michigan. When he came to Fred Hutch as a fellow in 1997, he concentrated on basic scientific discovery and translational research.
“I focused on AML in part because AML therapies had stagnated for decades,” he said. “It was an opportunity to ask important biological questions and more importantly, try to develop new therapies. Our standard of care for AML has not changed in nearly 50 years. We hope the new therapies we are developing will improve our approaches to treating AML.”
The novel therapies that Meshinchi’s lab are developing are in early-stage Phase 1 clinical trials; he is hoping to advance them to standard-of-care therapies. The bar is quite low: “For the particular type of infant AML that Stella had, survival is almost zero,” said Meshinchi. “In such high-risk diseases, any indication of efficacy can help advance these discoveries to upfront therapy quite quickly.”
Endowed chairs provide financial support for research. At Fred Hutch, donors can choose to endow a chair for a faculty member with a gift of $2 million or more. Fred Hutch currently has more than 50 endowed chairs, which allow donors to partner with scientists and clinicians and provide sustained, flexible support for forward-looking research. Endowments are a cornerstone of the Campaign for Fred Hutch, which is working to raise $3 billion to radically increase the pace and scale of innovation.
“We are fortunate to have someone as creative and dedicated as Soheil, who is determined to accelerate the pace of progress in treatment of pediatric AML and other cancers,” said Fred Hutch President and Director Thomas J. Lynch Jr., MD, holder of the Raisbeck Endowed Chair. “This endowed chair supports Soheil’s tireless efforts to forge cancer breakthroughs by harnessing the immune system to fight cancer.”
That innovative spirit was reflected in Dylan. His parents saw in Meshinchi someone whose curiosity reminded them of their son’s drive to understand the world. Dylan knew that Meshinchi was working on multiple fronts to push the science forward and help treat kids like him. "Dylan really liked the idea of the endowed chair and giving back,” said Burke. “He had many great ideas to contribute to our world if he could only have stayed with us longer.”
Bonnie Rochman is a senior editor and writer at Fred Hutch Cancer Center. A former health and parenting writer for Time, she has written a popular science book about genetics, "The Gene Machine: How Genetic Technologies Are Changing the Way We Have Kids—and the Kids We Have." Reach her at brochman@fredhutch.org.
Are you interested in reprinting or republishing this story? Be our guest! We want to help connect people with the information they need. We just ask that you link back to the original article, preserve the author’s byline and refrain from making edits that alter the original context. Questions? Email us at communications@fredhutch.org
Every dollar counts. Please support lifesaving research today.
For the Media