Project Stella  

Dr. Soheil Meshinchi | Fred Hutch Cancer Center

FOLR1 CAR T EARLY CLINICAL RESULTS —-> Read Dr. Meshinchi's Project Stella Impact Report

• At a Glance:

• 7 children treated in the first FOLR1-directed CAR T clinical trial.

• 4 achieved deep remission, with no measurable leukemia detected after treatment.

• Healthy blood production recovered, demonstrating the potential to attack leukemia while sparing normal blood-forming cells.

• More than $3.5 million raised by donors and foundations helped move this research from laboratory discovery to clinical testing.

• More funding is needed to continue the clinical program, treat additional children and help move this promising therapy toward Phase II.

• These are encouraging early results. Additional patients and longer follow-up are needed.

Read the full research update below:

When we shared our last newsletter, we were thrilled to announce that the first child had received the CAR T therapy developed through the Project Stella research program. Today, we can share an extraordinary early update from that clinical trial.  The first seven children have now been treated, and four achieved deep remission—meaning no detectable leukemia was found after treatment. Even more importantly, the treatment showed the potential researchers had hoped for: it targeted leukemia while preserving the children's normal blood-forming cells.

For children with this particularly aggressive form of AML, these early results represent an important step forward.

Why This Approach Is Different

One of the biggest challenges in treating AML with CAR T-cell therapy has always been finding something to target that is found on leukemia cells but not on healthy blood-forming cells.  Most potential targets are shared by both leukemia and normal cells. Targeting them can therefore destroy healthy blood cells along with leukemia.

Dr. Soheil Meshinchi and his team took a different approach. They first identified the unique genetic change that causes this particular form of leukemia, known as CBF-GLIS or RAM AML, which primarily affects infants and very young children. They then discovered FOLR1, a protein found on the surface of these leukemia cells but absent from normal blood-forming cells.  This gave the team something they had been searching for: a highly selective "bull's-eye" on the leukemia. They then developed CAR T cells programmed to recognize that marker and attack the leukemia.

In simple terms, they taught a child's own immune cells to recognize the leukemia while leaving healthy blood-forming cells alone.

From Discovery to Clinical Trial

What makes this milestone particularly meaningful is how quickly a laboratory discovery was translated into a treatment for children. After identifying FOLR1 as a potential leukemia-specific target, the Meshinchi Lab conducted the extensive laboratory and preclinical work necessary to develop and test the CAR T therapy. With the support of Project Stella and its donors, that work moved forward without having to wait years for traditional grant funding.

Within approximately four years—compared with the 10 years or more that drug development can often take—the team was able to launch the first-ever clinical trial of FOLR1-directed CAR T-cell therapy for children with this aggressive form of AML.

For a rare pediatric cancer with extraordinarily limited treatment options, that acceleration is significant. It is a powerful example of what philanthropic support can make possible when promising science cannot afford to wait.

Early Clinical Results Are Encouraging

Seven young children with relapsed or treatment-resistant AML have been treated in the first phase of the clinical trial. The children ranged in age from approximately 1½ to 4years old.  Four of the seven children experienced strong CAR T-cell expansion after treatment.

All four of those children achieved a deep remission, with no measurable leukemia detected in their bone marrow by day 28.

By comparison, the three children whose CAR T cells did not expand effectively did not respond to treatment.  This is an important finding. It tells researchers that getting the CAR T cells to successfully multiply and persist inside the child's body appears to be a critical factor in making the treatment work.

Just as Important: Healthy Blood Cells Were Spared

Perhaps the most significant finding is not only that the CAR T cells attacked leukemia, but that they did not cause the destruction of normal blood-forming cells that has historically limited CAR T therapy for AML.

All of the children recovered their normal blood production by day 36.

This provides the first prospective clinical evidence that targeting an antigen found specifically on leukemia cells can produce deep remissions without causing the expected damage to normal blood-forming cells.

This is precisely the challenge Dr. Meshinchi and his team have been working to overcome.

There Are Still Challenges Ahead

As exciting as these results are, this remains an early-stage clinical trial involving only seven children. There is much more to learn.  One child experienced significant inflammatory complication after receiving the initial higher dose of CAR T cells. Dr. Meshinchi's team subsequently lowered the dose, and the six children treated at the lower dose did not experience the severe cytokine-release or neurological complications seen with the first patient.  The researchers also observed an important form of leukemia resistance. One child who initially responded eventually relapsed with leukemia that no longer carried the target recognized by the CAR T cells. This suggests that, under the pressure of treatment, leukemia was able to escape by losing the marker the therapy was designed to recognize. Another child relapsed with leukemia that still carried the target. These experiences are providing researchers with important information about how leukemia can resist treatment—and how future therapies may need to be designed to prevent or overcome that resistance. While these results are encouraging, they are still very early. More patients and longer follow-up will be necessary to understand how durable the responses will be.

From a Laboratory Discovery to a Treatment for Children

Perhaps the most meaningful accomplishment of this work is how far it has come.

Researchers began with a question in the laboratory: Could we find something that exists on the leukemia but not on healthy blood-forming cells?  They found their answer, developed a CART-cell therapy around it, and ultimately brought that therapy into a first-in-human clinical trial.

Four of the first seven children achieved deep remission.

We cannot say that this treatment is a cure. But these early results provide something that has been desperately needed in AML: evidence that leukemia-restricted targeting is not just an idea, it can work in children.

What Comes Next

The next major milestone is the continued development of the clinical trial and, ultimately, a Phase I study.  Dr. Meshinchi plans to continue enrolling patients to gather additional data and help determine the optimal dose before moving into Phase II. At the same time, he is collaborating with Dr. Franco Locatelli and the Bambino Gesù Children's Hospital in Rome to expand clinical experience with this rare leukemia internationally.

The first clinical trial has also created something that will benefit research well beyond this particular therapy. The infrastructure, knowledge, and experience built through this trial can help accelerate the development of future pediatric AML therapies.

The Meshinchi Lab is already pursuing several promising directions, including next-generation CAR T Technology that could potentially improve the ability of CAR T cells to find leukemia throughout the body. The team is also developing approaches that can target two leukemia markers at once, including PRAME and WT1, which are found in RAM/CBF-GLIS and other pediatric AML subtypes.

These approaches could potentially expand precision immunotherapy to many more children.

This Is Why Project Stella Matters

The progress we are seeing today is the result of years of research, collaboration, and investment in a disease that has historically offered far too few options for young children.  Since 2018, the Project Stella community has raised more than $3.5 million to accelerate this work. That support helped move a promising laboratory discovery toward clinical testing and, ultimately, into the hands of children who desperately needed another option. The success of this CAR T program also provides a blueprint for what can come next. If researchers can identify unique targets created by the genetic changes driving other aggressive pediatric leukemias, we may be able to develop similarly precise therapies for those children as well.

That is the larger vision behind the work Project Stella has helped make possible: to move beyond simply treating leukemia and toward treatments designed around the biology of each child's disease.

And the need to continue that work is urgent.

A Thank You to Our Project Stella Community

None of this happens overnight. The journey from a laboratory discovery to a clinical trial and now to the first children achieving deep remission takes years of research, collaboration, expertise, and funding. When we shared our first CAR T milestone, we asked you to send hope to the little boy in Seattle who had just received his infusion. Today, we can share that this approach has now been tested in seven young children, with four achieving deep remission.

Dr. Soheil Meshinchi and the entire Project Stella team would like to extend a very special thank you to Children's Cancer Research Fund, its board, donors, and supporters for helping make this groundbreaking work possible. Their generous support provided a critical bridge that helped move this research from a laboratory discovery to the first-ever clinical trial of FOLR1-directed CAR T-cell therapy for children with this aggressive form of AML.

And thank you to the many families and foundations who made this work possible:

For a rare childhood cancer with extraordinarily limited treatment options, reaching this point is an extraordinary achievement. We are deeply grateful to everyone who believed in this work and supported it long before we knew what the outcome would be.

We are equally grateful to the families who have entrusted their children to this research and to the physicians, nurses, scientists, manufacturing specialists, research coordinators, regulatory experts, and collaborators whose dedication made each step possible.

But this milestone is not the finish line.

Researchers are continuing to enroll children in the clinical trial, determine the optimal dose, understand how to make CAR T cells expand more consistently, improve the durability of responses, and learn how to prevent leukemia from escaping treatment.

At the same time, the Meshinchi Lab is applying this same discovery strategy to other high-risk pediatric leukemias and exploring new technologies and targets that could ultimately benefit many more children.

We cannot yet know where this journey will ultimately lead. But we now have something incredibly important:

Hope grounded in science.

To everyone who believed in these children, supported this research, and helped Project Stella pushforward when there is no time to lose—we are profoundly grateful.

We will continue to work with urgency, determination, and above all else, hope.

On behalf of the children and families whose lives are at the heart of this mission, thank you!

                                 Future Research Updates

As the Pediatric AML Collaborative grows, future updates will highlight research and progress from investigators and institutions supported through Collaborative grants—providing a broader view of discoveries, treatments and clinical advances across pediatric AML.

The goal is not simply to fund more research. It is to help promising discoveries move faster—from the laboratory toward treatments for children.