Project Stella enables novel pediatric AML immunotherapies, potential cure

Fred Hutch's Dr. Soheil Meshinchi's lab identifies potential drug while also developing immunotherapy thanks to fundraising
The Siders family with Fred Hutch's Dr. Soheil Meshinchi
Ella Siders and her family with Fred Hutch physician-scientist Dr. Soheil Meshinchi (far right) at a fundraiser in Las Vegas last fall. Photo courtesy of Christina Siders

In the fall of 2016, Stella Novotny, two weeks shy of her third birthday, was diagnosed with acute myeloid leukemia (AML). Stella lived in New York, where she was first treated with chemotherapy and then a bone marrow transplant. Although the transplant appeared to work initially, Stella soon relapsed, which underscored the seriousness of her situation. 

“We understood the gravity from day one and thought she might have one more bite at this apple if she had any bites at all,” said Carryn McLaughlin, a close family friend who speaks on behalf of Stella’s family.

McLaughlin helped Stella’s parents do a comprehensive search for something, anything, that might prove helpful. Across the country, they found Soheil Meshinchi, MD, PhD, a pediatric hematologist/oncologist at Fred Hutchinson Cancer Center. Meshinchi thought Stella might have a recently discovered highly aggressive type of leukemia. This specific variety of leukemia, called RAM phenotype, is caused by a translocation — essentially a joining of two different genes, CBF and GLIS, that caused her leukemia and likely happened before Stella was born. “The fact that she made it to almost 3 with hardly any symptoms was very unusual,” said McLaughlin.

The CBF/GLIS translocation caused the leukemia cells to grow unchecked until there wasn’t enough room in Stella’s bone marrow to maintain a healthy balance of red and white blood cells and platelets. 

Stella’s family decided to move to Seattle so Stella could be under Meshinchi’s care. They uprooted their family from their Manhattan home in June 2016, shortly after she relapsed. At Fred Hutch, they toured Meshinchi’s lab. “They wanted to see what we do in the lab and see the biobank where we freeze leukemia cells so we can test drugs or grow those cells in mice,” said Meshinchi. Stella’s cells are preserved there, among more than 100,000 specimens collected from more than 3,000 patients. These cells, Meshinchi says, are "the engine that drives our research.”

Laboratory scientists often toil in isolation, far removed from patient care. But when Stella visited, she mugged for funny face photos with the lab employees, dancing around the lab. “If you walk over to the lab,” said Meshinchi, “you’ll see Stella’s picture.” 

Stella received two new drugs intended to stop the pathway creating the leukemia cells; they didn’t work. Then she became the sole person in a first-in-humans trial of a different drug, an immunotherapy directed at a protein called PRAME that was expressed in Stella’s leukemia. Because the drug hadn’t yet been administered to people, the initial doses were very low, too low to counter Stella’s skyrocketing leukemia counts. Meshinchi’s lab has since developed a more potent version of immunotherapy against PRAME.

Her death on Nov. 1, 2017 — three weeks after she celebrated her fourth birthday — crushed her family, Meshinchi, the lab. 

“We were fighting an uphill battle,” said McLaughlin, “doing the most with the information we had while knowing we had very little information because Stella was the only patient at the time being studied.”

Young Stella Novotny, a pediatric patient in hospital.
Stella Novotny, a pediatric AML patient whose death inspired the creation of Project Stella, a philanthropic initiative to support immunotherapy research by Fred Hutch physician-scientist Dr. Soheil Meshinchi Photo courtesy of the Novotny family

Launching Project Stella

Soon after Stella’s death, her parents, Casey and Jed Novotny, decided to try to wring some sort of meaning from their daughter’s experience. They wanted to raise money to find a treatment, hopefully a cure, for Stella’s type of leukemia, so they launched Project Stella, a philanthropic initiative at Fred Hutch.

It’s an unfortunate truth that pediatric cancer receives a fraction of the funding that adult cancer does. Just 4% of all federal cancer research dollars goes toward pediatric cancers. It’s a function of scale: cancer strikes far fewer children than adults. But statistics mean nothing when it’s your child who is diagnosed. To make matters worse, pharmaceutical companies can be reluctant to invest in drug development for diseases that affect small numbers of people. The disparity in funding spurs some families to take on an additional role of fundraiser even as they’re grieving an unspeakable loss or at the same time that they’re supporting and advocating for their child, physically and emotionally. To these families, the need to raise money to support research for their child’s disease can be a matter of life or death. 

Related Information

Learn more about the FOLR-1 CAR-T clinical trial.

That also means families can have outsized impact. Project Stella has raised more than $2 million and has reshaped Meshinchi’s approach to the rare subtype of pediatric AML that attacked Stella's tiny body. The support raised through Project Stella has fueled the development of a new immunotherapy to treat this cancer — the first time that philanthropic donations have been used to develop a drug at Fred Hutch — and an associated CAR T clinical trial, which could revolutionize treatment of this subtype that strikes fewer than 30 babies and toddlers in the U.S. each year. “A single child transformed how we think about disease and how we develop therapies,” said Meshinchi. 

Stella’s cancer was caused by a genetic mix-up that converts normal cells into cancerous ones. “It’s so rare that we didn’t know it existed until five or six years ago,” said Meshinchi. Pinpointing the genetic change allowed Meshinchi to understand the biology of Stella’s disease, which in turn allowed him to explore potential targets that are uniquely expressed by the genetic translocation. 

With support from Project Stella, Stella’s particular translocation has been introduced to healthy cord blood stem cells in culture, transforming these cells into leukemia. These studies have helped Meshinchi’s lab discover a novel target called FOLR-1, a gene that helps make a protein, folate receptor alpha, involved in DNA repair. FOLR-1 is not normally expressed on healthy white or red blood cells or platelets. But FOLR-1’s stamp was all over Stella’s leukemia cells.

Meshinchi decided to go after that target. 

Ella Siders, a pediatric AML patient
Ella Siders, a pediatric AML patient whose family is supporting Dr. Soheil Meshinchi's research into new treatments for her disease. Photo courtesy of Christina Siders

Desperately seeking options

At 4 years old, Ella Siders is the longest known survivor of the type of pediatric AML that Stella had. Diagnosed in 2019 at 14 months, Ella celebrated her three-year “re-birthday” on Feb. 18 — marking the date in 2020 when she got a bone marrow transplant that wiped out her disease. Like most kids with AML, she endured a powerful chemotherapy regimen leading up to her transplant; after each cycle, she’d develop a bacterial infection or fungal pneumonia. Following the transplant, she grew critically ill from graft-vs.-host disease, as the new donor cells attacked her gut so mercilessly that part of her intestines leaked into her diaper. 

The chance of relapse remained high, so Christina and Joe Siders, Ella’s parents, were ecstatic to get a phone call from Meshinchi in October 2020 telling her that initial research data had showed that luvelta was effective against pediatric AML. “You never like to see a doctor calling you, but this was great news,” said Christina Siders. 

Meshinchi was updating Siders because they are some of his biggest supporters. The Siders family lives outside Chicago, where Ella was treated. But Ella’s oncologist consulted early on with Meshinchi because he is widely considered the global expert on this particular cancer. And Siders sought his advice as Ella’s transplant date approached. In one conversation, he mentioned Project Stella, which prompted Siders to reach out to Stella’s family. At the time, they had raised $750,000. Siders circled back with Meshinchi.  

“What are the timelines for what you have in the works?” she asked him. 

Meshinchi responded that it could take up to five years. 

“That’s not fast enough,” she replied. “What do you need to make this move faster?”

Additional funding would give Meshinchi’s lab the ability to tackle the disease on parallel paths: researching existing drugs that might be effective treatments while at the same time developing a CAR T immunotherapy with the potential to cure the cancer. 

With that vision in mind, Siders and her extended family — in partnership with Stella’s family — got to work. Fundraising totals ticked up, up, up as they donated, other families donated, and GoFundMe campaigns raised additional money. In all, more than 450 people came together over five years to raise $2 million, with additional gifts expected.  

Learn more about Project Stella and support its mission.

Discovering a novel target

The infusion of funding helped Meshinchi’s lab dive into the painstakingly slow process of developing a CAR T therapy with the goal of curing, not simply treating, the cancer. At the same time, they began data mining and uncovered a few potential drugs that might hit the FOLR-1 target. The process of trying to figure out what existing drugs might work against a particular disease happens largely on a computer as software serves up suggestions of drug compounds that may be effective against identified targets such as FOLR-1. That target is also highly expressed in ovarian cancer, so Meshinchi suspected some drugs for that cancer could be helpful for Stella’s type of leukemia. 

One of the drugs identified as a possible match is manufactured by Sutro Biopharma, a South San Francisco biotech company that gave Meshinchi’s lab a supply of luvelta, its ovarian cancer drug, to test in preclinical studies; after encouraging results, Sutro provided access to luvelta on a compassionate use basis to children who had relapsed and had no hope of a cure.  The children’s response to the drug was remarkable — everyone treated with luvelta responded to the drug and experienced limited side effects. In some cases, luvelta eliminated the disease completely.    

In 2021 and 2022, Meshinchi presented data at the annual meeting of the American Society of Hematology indicating that luvelta showed promise against Stella’s type of leukemia. After his 2021 presentation, Sutro began fielding requests from all over the world for its drug. In the past two years, Sutro has provided luvelta, which is still in clinical trials, for free to 25 infants and toddlers on a compassionate use basis — a designation that patients and their doctors request from the FDA for drugs unapproved for their condition when no other treatments exist.   

Luvelta doesn’t suppress the immune system as does chemotherapy; instead, it targets a protein that is expressed only on the cancer cell, leaving intact healthy cells’ ability to fight infection.  This reduces toxicity observed with conventional chemotherapy. In line with the provisions of compassionate use, luvelta is approved for use only in those patients who have relapsed. Sutro is planning a clinical trial for luvelta, hoping to eventually receive approval to use it as a front-line therapy in Stella’s type of leukemia.

The decision to supply luvelta first to Meshinchi at Fred Hutch and then to children in need, wherever they are, was an easy one, says Sutro CEO Bill Newell. Newell was no newcomer to Fred Hutch; in 2019, he participated in Fred Hutch’s Climb to Fight Cancer as part of a group of 27 biotech researchers, executives and investors that raised $1.6 million for cancer research at Fred Hutch. "In the time we’ve been allowing this drug for compassionate use, we’ve treated probably every child diagnosed with the RAM phenotype,” said Newell. “It’s a very small niche population."

Luvelta is being developed primarily to treat women with late-stage ovarian cancer. It’s a class of drugs known as an antibody drug conjugate, a combination treatment that’s like a two-in-one punch: an antibody targets an antigen — a particular site on a tumor cell — and brings with it a “linker,” a means of attaching the antibody warhead to the antibody itself, plus a cytotoxic payload. As the antibody enters the tumor cell, the linker detaches from the antibody and the warhead is activated. End result if all goes as planned? Death to cancer cells. 

The drug has been evaluated at varying doses in 100 women with late-stage ovarian cancer. Recently reported data showed that 44% of patients responded to the higher dose. Sutro is on the verge of starting a clinical trial to seek FDA approval for luvelta to treat a subset of ovarian cancer. “This drug was not created to treat leukemia; it was created to treat solid tumors,” said Newell. "From our standpoint, it’s a very pleasant surprise to hear it was quite effective for helping these kids for whom most existing leukemia drugs don’t work.” 

A sign honoring Stella Novotny in Fred Hutch's Steam Plant
Fred Hutch formally recognized the essential role that families play in moving research forward with the naming of the Project Stella Research Floor. Fred Hutch file photo

Because Ella is in remission, she hasn’t needed to try luvelta. But the likelihood of relapse is high; Siders was told there was a 93% chance post-transplant. "As parents, we were told to wait and pray and hope it wouldn’t come back,” said Siders. “It’s impossible to sit and do nothing. We got involved with Project Stella so if Ella relapses, there are options for her. This has given us some place to channel our anxiety and fear.”

A ‘guided missile’ for cancer

What really motivates Siders is the prospect of a clinical trial for the Hutch-developed immunotherapy. “The CAR T is exciting because it trains the body to fight the cancer, and it's more likely to be curative long-term,” she said. "Kids wouldn’t necessarily need round after round of toxic chemo or even a transplant."

CAR T therapy harnesses a patient’s immune system to do the hard labor of fighting cancer. T cells are collected from patients, then engineered to express an antibody of interest. That antibody is then introduced to the patient via a vector, or virus, that "infects" the T cells with the antibody to help the patient’s T cells recognize the leukemia cells and kill them. “It’s like providing a guided missile,” said Meshinchi. 

But vectors require significant investment; this one cost about $1 million to generate. The development and engineering process is rigorously overseen to make sure everything is sterile, and that the CAR T kills the cells it’s supposed to and not the ones it should leave untouched. Then the therapy and its detailed protocols need to be submitted to the FDA for approval in order to proceed with a research study in humans. Meshinchi hopes approval will come this summer. “Since the number of patients seen a year with this is so small, there’s no interest from drug companies to support this. That’s where fundraising is critical,” said Meshinchi. "The biggest hurdle to this work is financial.”

Siders puts it in starker terms. "Nobody seems to care,” she said. "As a parent, it’s absolutely infuriating and heartbreaking. When it comes to rare disease subtypes, no one really cares at all. If we don’t raise the money, none of this research would happen. If Dr. Meshinchi wasn’t researching this, no one else would be.”

Siders keeps the handful of other families whose children share Stella and Ella’s mutation updated on the latest milestones in Meshinchi’s lab. Kids like Aspen, who has responded so well to luvelta that she hasn’t needed to undergo a second transplant, and Indiya, who hasn’t responded as well. “We are connected with other families throughout the world fighting this form of AML and these therapies, and this research gives them hope,” she said. “We all just want our children to grow up."

Recently, Fred Hutch formally recognized the essential role that families play in moving research forward with the naming of the Project Stella Research Floor, which recognizes these families’ impact on advancing science and serves as a permanent testimonial to Stella. 

“Stella was such a powerful human in the time she was on this earth,” said Carryn McLaughlin, Stella’s mom’s business partner in their financial advising firm. Serving as the public face of Project Stella is too painful for Stella’s parents, so McLaughlin has stepped up, doing grassroots fundraising and working with Meshinchi on grant-writing. 

“The only way for a cure to happen is for someone to make this their passion project," she said.  “I don’t have kids of my own,” she said. “This is meaningful and brings me joy. I want to ensure that the legacy of this 4-year-old doesn’t end.”

Ella is now the same age that Stella was when she died. Several months ago, Ella asked her mother a question that has no good answer. “What if my cancer comes back, mama?” Siders was silent, stunned. 

“Once I caught my breath,” Siders recalled, “I said that’s not going to happen. And if it does, we will fix it. That’s why we’re working on Project Stella.” 

Four-year-olds believe their mothers. Ella didn’t probe further.

bonnie-rochman

Bonnie Rochman is a staff writer at Fred Hutchinson 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.

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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

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