Fulfilling the promise of cell and gene therapies for children

The Center for Cancer and Immunology Research (CCIR) at Children’s National Hospital remains at the forefront of pioneering treatments for children with compromised immune systems. Under the leadership of Catherine Bollard, M.B.Ch.B., M.D., the center has developed cutting-edge cell and gene therapies that have demonstrated remarkable promise in clinical settings. However, the lack of a clear commercialization pathway for these therapies has presented significant challenges, a gap that Michael Keller, M.D., who leads the antiviral immunotherapy program, is actively seeking, along with other Faculty within the CCIR, to bridge through innovative partnerships and initiatives.

Over the past decade, Dr. Keller’s work has focused on adoptive T-cell therapy, a novel approach that uses immune cells to restore immunity in patients with severe viral infections or cancers. For children who have undergone bone marrow transplants, where immune recovery can be delayed or incomplete, these therapies offer hope in preventing and treating life-threatening infections. “Since 2013, we have built a robust program centered on antiviral T-cell therapy, treating pediatric patients whose immune systems are severely compromised after transplant,” Dr. Keller explains. The approach utilizes T cells banked from healthy donors — either related or unrelated — allowing the cells to be administered to patients as needed, similar to how blood products are stored and used.

In a Phase II multi-center national trial, led by Dr. Keller and funded by the California Institute for Regenerative Medicine, the team treated 51 pediatric patients across 22 hospitals in the U.S. The trial reported a 65% response rate, a significant outcome given that these children had previously failed conventional therapies. “These are critically ill patients, so achieving this level of response is a testament to the efficacy of the therapy,” says Dr. Keller. The study, recently published in Nature Communications in two back-to-back publications, highlights the potential of adoptive T-cell therapy to transform care for immunocompromised children.

The hospital has been instrumental in disseminating this expertise and technology to other institutions. A notable success story is their collaboration with Cincinnati Children’s Hospital Medical Center, which has treated over 1,000 patients since adopting Children’s National’s protocols in 2017.

However, despite the demonstrated efficacy, these therapies face substantial barriers to broader adoption. Regulatory challenges, in particular, have slowed progress toward commercialization. “It’s frustrating that this therapy, which we’ve been developing and refining for years, remains boutique,” Dr. Keller acknowledges. “It should be more widespread, but the regulatory hurdles keep it from becoming standard of care.” The therapies remain classified as Investigational New Drug (IND) products, requiring special FDA permissions for each use, alongside rigorous monitoring and oversight.

While Dr. Keller’s team at Children’s National is among the few in the country offering these therapies, the broader adoption of pediatric cell and gene therapies has been hindered by the complexity of regulatory approval. Only recently, a similar T-cell therapy was approved by the European Medicines Agency (EMA), signaling that progress is possible, though it remains elusive in the U.S. To overcome these barriers, industry collaboration is essential.

Recognizing this urgent need, Dr. Bollard and her CCIR team, including Dr. Keller and Patrick J. Hanley, Ph.D., recently convened a think tank at the Children’s National Research and Innovation Campus, bringing together experts from the biotech industry, regulatory agencies and the academic community. The goal was to explore potential pathways to accelerate the commercialization of pediatric cell and gene therapies. “We need a clear route to FDA approval and greater support from industry partners,” Dr. Keller stresses. The think tank aimed to align these stakeholders, advocating for more streamlined regulatory processes and sustainable commercialization strategies.

Dr. Keller’s vision for the future of pediatric immunotherapy is clear. By establishing closer partnerships with industry and regulatory agencies, he hopes to see therapies like adoptive T-cell treatment become a standard part of care for children with compromised immune systems. “We’ve proven the feasibility and efficacy of these treatments,” he states. “Now, it’s about getting them over the finish line, so they are accessible to every child who needs them.”

As the field of pediatric cell and gene therapies continues to evolve, the work of Dr. Keller and the entire CCIR team stands as a beacon of innovation. With sustained efforts to address the current barriers to commercialization, the hope is that these therapies will soon reach more children in need, fulfilling their potential to transform pediatric care.