A Breakthrough in Stem Cell Transplantation: Stanford Medicine’s Antibody Therapy Offers Hope for Fragile Patients
In a groundbreaking advancement for regenerative medicine, researchers at Stanford Medicine have developed a revolutionary antibody-based therapy that enables safe and effective stem cell transplants without the use of toxic chemotherapy or radiation. The results, recently published in Nature Medicine, come from a phase 1 clinical trial that focused on patients with Fanconi anemia, a rare genetic disorder that has long made traditional stem cell transplantation both dangerous and often fatal. This innovative approach marks a transformative step in the field of bone marrow transplantation, offering new hope not only to Fanconi anemia patients but also to individuals suffering from a range of inherited and blood-related diseases.
Reimagining Transplant Conditioning
Before any stem cell transplant, the patient’s diseased or defective bone marrow must be cleared to make room for the donor’s healthy stem cells. Traditionally, this conditioning process involves high-dose chemotherapy or radiation—treatments that are toxic to both cancerous and healthy cells. These regimens can cause severe side effects such as organ damage, infertility, and even secondary cancers. For individuals with Fanconi anemia, who already have an impaired ability to repair DNA damage, these traditional methods pose life-threatening risks.
To overcome this challenge, Stanford scientists turned to an antibody-based strategy. The therapy centers around an antibody called briquilimab, which targets CD117, a protein present on the surface of blood-forming stem cells. By binding to CD117, briquilimab selectively removes the patient’s existing stem cells without the need for radiation or genotoxic chemotherapy. This allows donor cells to engraft safely while sparing the patient from the harmful consequences of conventional conditioning methods.
According to Dr. Agnieszka Czechowicz, assistant professor of pediatrics and co-senior author of the study, “We were able to treat these really fragile patients with a new, innovative regimen that allowed us to reduce the toxicity of the stem cell transplant protocol. Specifically, we could eliminate the use of radiation and busulfan chemotherapy, with exceptional outcomes.”
The trial’s results have exceeded expectations. All three pediatric patients with Fanconi anemia who received the antibody-based treatment successfully underwent transplants and have remained healthy for over two years.
A Lifeline for Fanconi Anemia Patients
Fanconi anemia is a devastating inherited condition that disrupts the body’s ability to repair damaged DNA. This leads to progressive failure of the bone marrow—the body’s blood cell factory—and often results in severe anemia, frequent infections, and excessive bleeding. By the time affected children reach adolescence, their bone marrow is typically incapable of producing sufficient blood cells, making a transplant their only chance for survival. Yet, traditional chemotherapy or radiation-based transplants can trigger complications, secondary cancers, or fatal toxicity.
Dr. Rajni Agarwal, professor of pediatric stem cell transplantation and co-first author of the study, emphasized the life-saving implications of this therapy. “If they don’t get a transplant in time, Fanconi anemia patients’ bodies eventually will not make blood, so they die of bleeding or infections. The reason I am so excited about this trial is that it is a novel approach to help these very vulnerable patients.”
The antibody therapy safely removed old stem cells while preserving other tissues, thus preparing the patients’ bodies for transplantation with minimal risk. Two years after the procedure, all three children demonstrated nearly 100% donor cell chimerism, meaning their bone marrow was fully replaced by the donor’s cells. None experienced graft rejection or serious complications, an outcome that represents an extraordinary milestone for Fanconi anemia treatment.
Expanding Donor Possibilities
One of the long-standing barriers in stem cell transplantation has been the difficulty in finding fully matched donors. Traditionally, up to 40% of patients could not undergo transplants simply because compatible donors were unavailable. To address this challenge, the Stanford team combined the antibody therapy with an innovative donor cell preparation technique pioneered by Dr. Alice Bertaina.
In this approach, donor bone marrow is enriched for CD34+ cells, which are blood-forming stem cells, while alpha/beta T-cells—immune cells responsible for graft-versus-host disease—are removed. This allows transplants to be performed safely even from half-matched (haploidentical) donors, such as parents. “We are expanding the donors for stem cell transplantation in a major way,” said Agarwal. “Every patient who needs a transplant can now get one.”
This strategy not only broadens the donor pool but also makes the process safer and more accessible to families worldwide who previously faced the impossible task of finding a perfect match.
Ryder’s Remarkable Recovery
The first patient to undergo this new antibody-based transplant was Ryder Baker, an 11-year-old from Texas diagnosed with Fanconi anemia. In early 2022, Ryder received the treatment at Lucile Packard Children’s Hospital Stanford. Within weeks, his new donor stem cells had taken root, and his health began to improve dramatically.
His mother, Andrea Reiley, described the transformation: “He was so tired, he didn’t have stamina. It’s completely different now. His Fanconi anemia doesn’t slow him down like it used to.”
Today, Ryder is thriving—playing soccer, attending school, and enjoying a life that once seemed out of reach. His story stands as a powerful testament to the potential of this therapy to change lives.
Building on Decades of Research
The foundation for this achievement was laid nearly two decades ago when Czechowicz, as an undergraduate working with Dr. Irving Weissman, began studying blood-forming stem cells and the role of CD117. Their early experiments in mice demonstrated that antibodies could deplete stem cells without radiation or chemotherapy. Over time, with contributions from Dr. Matthew Porteus and collaborations across institutions such as UCSF, St. Jude Children’s Research Hospital, and Memorial Sloan Kettering, the concept evolved from animal models to clinical reality.
Funding from the California Institute of Regenerative Medicine, the Fanconi Cancer Foundation, and anonymous donors helped make the clinical trial possible. The antibody briquilimab was provided by Jasper Therapeutics, which partnered with Stanford to bring the therapy into human testing.
A Safer Future for Transplants
The early success of the phase 1 trial has spurred a larger phase 2 clinical study now underway at Stanford, enrolling more children with Fanconi anemia. Researchers are also exploring whether this antibody-based approach could benefit patients with other inherited bone marrow failure syndromes, such as Diamond-Blackfan anemia.
While patients with blood cancers will likely still require some form of chemotherapy or radiation to eliminate malignant cells, the team is optimistic that this therapy—or future generations of similar antibodies—could make transplantation safer for older or medically fragile patients who cannot tolerate conventional regimens.
Dr. Agarwal envisions a future where such non-toxic conditioning regimens become standard: “When I counsel families, their eyes start to shine as they think, ‘OK, we can avoid the radiation and chemo toxicity.’ It changes everything.”
Conclusion: A New Era in Regenerative Medicine
Stanford Medicine’s antibody-based conditioning therapy represents more than a medical innovation—it embodies a paradigm shift in how stem cell transplants can be performed. By replacing radiation and chemotherapy with a precisely targeted antibody, researchers have not only safeguarded patients’ lives but also broadened access to life-saving transplants.
For patients like Ryder, and countless others awaiting treatment, this discovery opens the door to a future where curative transplants are not defined by toxicity or limited by donor availability. As Czechowicz noted, “We were optimistic that we would get here, but you never know when you’re trying a new regimen. We’ve been surprised by how well it’s worked.”
This landmark achievement ushers in a new era—one where science and compassion converge to give the most vulnerable patients a renewed chance at life.
Story Source: Stanford Medicine.
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