Uruguay Builds Its Own CAR T-Cell Program for Children With Leukemia

In a small South American nation of roughly 3.4 million people, a team of pediatric hematologists has achieved something that many larger countries have struggled to do: manufacture and deliver genetically engineered cancer-fighting immune cells to children with relapsed leukemia, entirely within their own borders and at no cost to families. Writing in Frontiers in Hematology, researchers from the Pérez Scremini Foundation in Montevideo, together with colleagues from Barcelona, describe how Uruguay launched an academic CAR T-cell program for childhood leukemia and lymphoma, offering a striking counterpoint to the top-down strategies pursued elsewhere in Latin America.

The commentary responds to a recent report by Guerino-Cunha and colleagues documenting Brazil’s efforts to establish a national CAR T-cell program. CAR T-cell therapy, which involves reprogramming a patient’s own T lymphocytes to recognize and destroy CD19-positive cancer cells, has transformed outcomes in relapsed and refractory B-cell acute lymphoblastic leukemia since the landmark tisagenlecleucel trials. Yet the commercial products remain extraordinarily expensive, with costs estimated to reach as much as 500,000 US dollars per patient. Uruguay, despite being classified as a high-income country, found that its national health budget simply could not absorb those prices, a predicament shared by Brazil and other neighboring nations.

Before the new program existed, only one Uruguayan child had ever received CAR T-cell therapy, and that single treatment required referral to a center abroad. Access, the authors note, mirrored the difficult scenario described in Brazil: judicial litigation, bureaucratic delays, and private fundraising campaigns to cover overseas costs. The contrast between the two countries is stark in scale. Brazil is the largest and most populous nation in South America, while Uruguay is the second smallest, with a highly centralized population. That geography, it turns out, became an unexpected asset.

Where Brazil’s CAR T-cell infrastructure has developed primarily through a top-down model promoted by national authorities and major international collaborations, Uruguay took the opposite route. The clinical need was identified directly by frontline pediatric oncologists and patient advocates, who mobilized charitable funding to support an autonomous point-of-care manufacturing strategy. The program was built from fundraising, without direct initial funding from national authorities, and relies on the automated cliniMACS Prodigy platform installed inside a certified Good Manufacturing Practice facility on the foundation’s own premises.

The product itself is a second-generation anti-CD19 CAR T-cell construct generated with a Miltenyi lentiviral vector and incorporating a 4-1BB costimulatory domain, the same architectural principle underlying approved commercial therapies. Comprehensive technical transfer and training of clinical and laboratory personnel were secured through academic collaboration with Hospital Sant Joan de Déu and Hospital Clínic in Barcelona. Uruguay also brought solid baseline infrastructure to the challenge, including established experience in hematopoietic stem cell transplantation, apheresis, advanced cell processing, and highly specialized supportive care, with immediate access to a referral pediatric intensive care unit.

The program launched in August 2025 with the infusion of its first pediatric patient. Offered as an academic research study, the clinical protocol was approved by the Hospital Pereira Rossell Ethical Committee and national regulatory offices, and therapy is provided free of charge regardless of whether families hold public or private insurance. Between August 2025 and May 2026, five patients were treated: four children and one young adult who had relapsed with acute lymphoblastic leukemia originally diagnosed during adolescence. Four had ALL and one had non-Hodgkin lymphoma. All received a standardized lymphodepletion regimen of cyclophosphamide and fludarabine, followed by infusion of fresh, non-cryopreserved CAR T-cells at a target dose of 3 million cells per kilogram.

The early safety profile was demanding but manageable. Four patients developed grade 3 cytokine release syndrome, the systemic inflammatory reaction that occurs when engineered T-cells activate en masse, requiring tocilizumab and temporary admission to the pediatric intensive care unit. Three patients developed immune effector cell-associated neurotoxicity syndrome, another well-recognized toxicity of CAR T-cell therapy. In every case the toxicities resolved without residual neurological or systemic sequelae. More striking are the efficacy signals: at the time of the report, all five patients remain in complete clinical remission and are negative for measurable residual disease by flow cytometry, showing the persistent B-cell aplasia that indicates the engineered cells remain biologically active. The authors caution that these outcomes are preliminary given the tiny sample size and short follow-up.

One of the most consequential technical advantages lies in logistics. Because the cells are manufactured on-site and infused fresh rather than cryopreserved, the program achieved a vein-to-vein time, the interval from leukapheresis to infusion, of less than 12 days. Commercial products, which must be shipped internationally and frozen, still average 100 to 150 days between collection and infusion. For patients with aggressive relapsed disease, that difference can be decisive. The centralized pediatric cancer care system, funneled through a single institutional partnership between the Pérez Scremini Foundation and Hospital Pereira Rossell, eliminates the bottlenecks of long-distance cell transport and allows seamless referral to a single manufacturing center.

The path from concept to clinic was far slower than anticipated, however. Although the program was conceived in 2021, the first patient was not infused until 2025, a four-year delay caused by barriers strikingly similar to those described in Brazil: bureaucratic hurdles in importing specialized equipment, lengthy national regulatory approvals for cell therapy products, complex global procurement of viral vectors, and the meticulous validation required for a local GMP facility operating under strict international standards. Maintaining a decentralized point-of-care framework also demands a robust, continuous quality management system to satisfy both international cellular therapy standards and evolving local regulations.

Scalability and sustainability remain open questions. Current manufacturing capacity covers national pediatric demand, estimated at roughly three to five candidates per year based on standard clinical indications, but expanding to adult indications or other hematological malignancies would introduce substantial challenges. The entire operational model depends on imported specialized reagents, disposables, and viral vectors, leaving it exposed to global market bottlenecks and customs delays, and formal long-term financial sustainability has not yet been achieved, with reimbursement mechanisms from national authorities still under negotiation. The authors also acknowledge that their model’s favorable conditions, small patient volume, short travel distances, and a single centralized referral center, limit its direct generalizability to larger or geographically dispersed health systems. Even so, the Uruguayan experience demonstrates that a public-private and charitable partnership can implement an efficient, academic, point-of-care CAR T-cell program in Latin America, offering a bottom-up blueprint for countries where commercial pricing puts these life-saving therapies out of reach.

Subject of Research: Academic point-of-care CAR T-cell therapy access for pediatric leukemia and lymphoma in Uruguay

Article Title: Commentary: “Bridging innovation and equity: the evolving landscape of CAR T-cell therapy access in Brazil” The Uruguayan pediatric experience

Article References: Pereira, M. I., Barrios, M., D’ Andrea, L., Ibarra, M., Rives, S., & Castillo, L. (2026). Commentary: “Bridging innovation and equity: the evolving landscape of CAR T-cell therapy access in Brazil” The Uruguayan pediatric experience. Frontiers in Hematology, 5, Article 1891877. https://doi.org/10.3389/frhem.2026.1891877

Image Credits: AI Generated

DOI: 10.3389/frhem.2026.1891877

Keywords: CAR T-cell therapy, pediatric oncology, acute lymphoblastic leukemia, point-of-care manufacturing, Uruguay, Latin America, health equity, cell therapy, lymphoma, cytokine release syndrome, GMP facility, health economics