Pediatric cancer research typically spans decades, with very few treatments being brought to children who urgently need them. In fact, only 3 drugs have been approved for childhood cancer in over 30 years. We are desperate to change the narrative for these kids, who are now given a dismal 8% chance of survival, despite toxic and largely ineffective treatment protocols.
Inspired by the overwhelming response to previous gifts, a generous anonymous donor is offering a third $100,000 challenge. Every dollar donated between February 1 and June 30, 2022 will be matched dollar for dollar! Please help us cross the finish line by donating today! Remember, 100% of all donations go directly to Project Stella research at Fred Hutch (501c3 non-profit).
Thank you for fighting with us.
Promising advances are being made on several fronts by Dr. Soheil Meshinchi and his team at the Fred Hutchinson Cancer Research Center.
Project Stella’s FOLR-1 CAR T is moving along quickly, at a typically un-heard of pace in pediatric cancer research. As a quick review, CAR T therapy is re-educating the patient’s own immune cells to recognize and destroy cancer cells. For this, immune cells are removed from a patient, armed with new proteins that allow them to recognize cancer, expanded, and given back to the patient in large numbers. These cells persist in the body, becoming “living drugs.” The first and most critical part of this work, the clinical vector creation for Project Stella’s FOLR-1 CAR T has been completed (THANK YOU). The next and the final step is “process engineering,” where the vector undergoes rigorous screening and testing to meet FDA clearance for clinical trial. We are on track to meet the deadline to launch a clinical trial in Q3/Q4 2022. The FOLR1 CAR T would provide a potentially curative treatment for various aggressive forms of pediatric cancers - not just AML-RAM. And it would potentially spare children from toxic therapies in the first place. This is our primary focus and is the driver of our plea for additional funds!
STRO-002 has now been administered successfully in 10 patients, with more children waiting to receive it. Despite vast differences in disease burden and stage of treatment, all patients showed positive, objective response and reduction in disease, without side effects. Getting a new, TARGETED drug to a child usually takes decades. We accomplished this through Project Stella in just over a year.
A new drug from Elucida is positioned to begin pediatric trials this year through the TACL (Therapeutic Advances in Childhood Leukemia & Lymphoma) consortium. The pre-clinical data regarding the efficacy of this drug against AML-RAM is incredibly promising. We are eager to add this drug to future protocols in the next 6-12 months.
CAR T cell therapy is a tailored form of immunotherapy that works by modifying the body's own T cells, a type of immune system cell that hunts and destroys abnormal cells. Scientists harvest T cells from patients, genetically alter them, then infuse the resulting CAR T cells into patients to attack cancerous cells. The CAR T cells then act as a "living drug" against cancer cells. When they come in contact with their targeted antigen on a cell, CAR T cells bind to it and become activated, then proliferate and become cytotoxic. In other words, they are cancer-fighting smart missiles.
Creating an effective CAR T is contingent on first identifying a suitable target. For safety, CAR T cells are engineered to be specific to an antigen expressed on a tumor that is not expressed on healthy cells. This is another reason genomic sequencing is so critical. Under the leadership of Dr. Meshinchi, sequencing has become part of pediatric AML protocol - advanced significantly in partnership with the LLS PEDAL initiative. Sequencing helps us understand the mutations underlying the disease, so vulnerabilities can be identified. As a result of Project Stella and the Hutch having the largest repository of pediatric leukemia samples, the Meshinchi Lab has identified several proteins that are highly expressed in AML RAM, like FOLR-1. Because FOLR-1 is found in high expressions on the outside of the cancer cell, it is ideally suited for immunotherapies. Moreover, it is not found on healthy cells.
Image: Leukemia & Lymphoma Society (LLS)
Dr Meshinchi gives a frank summary of why Project Stella has achieved major milestones in such a short time and why the next phase of CAR T cell therapy is critical to finding a cure for this devastating form of AML.
Graft-versus-host disease (GVHD) is a potentially serious complication that arises from stem cell/bone marrow transplants. GVHD occurs when the donor’s T cells (the graft) view the patient’s healthy cells (the host) as foreign, and attack and damage the patient’s cells. GVHD can be mild, moderate or severe and in some cases, it can be life-threatening. Ella battled moderate/severe GVHD in her gut shortly after transplant, the scariest and most difficult part of her treatment. She was unable to eat, drink, or even lift her head for weeks. She wasted away and was in constant pain as the walls of her intestine were shredded by her donor’s cells. Healing took several months, three of which were inpatient, and it very nearly killed her.
Sounds awful, right? But here’s the thing. GVHD can also promote something called graft vs. leukemia (GVL). Basically, the same donor cells that attack the patient also search out and destroy leukemia lurking in the patient’s body. Doctors walk a tight rope of letting just enough GVHD into the patient to cause GVL, without allowing the GVHD to run rampant. For some forms of leukemia, a transplant is strong enough to ensure remission, so GVHD is prevented as much as possible. But for AML-RAM, GVHD is almost essential to secure remission. Nothing about that fact feels right. It means that though kids may survive, it is unlikely they will thrive. We have said repeatedly that ‘Ella may need a lung and heart transplant down the road, but at least she’ll be alive.’ That is a bitter pill to swallow. And that is why it is so critical for us to continue pushing for better, more tailored treatments through Project Stella.