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

Introduction

Recently, Guerino-Cunha et al. described the successful implementation and systemic challenges in establishing a chimeric antigen receptor (CAR) T-cell program in Brazil (1). As alternative models of advanced cell therapy emerge across Latin America in parallel (2), we would like to comment on the development and implementation of an academic CAR T-cell program for childhood leukemia and lymphoma in Uruguay.

Uruguay is classified as a high-income country. However, like Brazil and other neighboring nations, its national health budget cannot absorb the high commercial costs of CAR T-cell products—which can reach an estimated USD 500,000 per patient— (3). So, the operational and structural context between the two nations is markedly contrasted. While Brazil is the largest and most populous country in South America, Uruguay is the second smallest, with a highly centralized population of approximately 3.4 million inhabitants.

In Uruguay, the care of pediatric oncology patients is centralized and delivered via a formal, long-standing partnership between the Pérez Scremini Foundation (FPS) and Hospital Pereira Rossell, the national pediatric public referral center (4). In 2021, a comprehensive strategy was launched to improve clinical outcomes in childhood acute lymphoblastic leukemia (ALL). This strategy combined access to advanced molecular diagnostics, the availability of new targeted drugs and academic CAR T-cell program. Based on standard clinical indications, we estimated that approximately 3 to 5 pediatric patients per year are candidates for CAR T-cell therapy in Uruguay.

Program development and methodology: bottom-up vs. top-down

An academic, decentralized point-of-care (POC) manufacturing model was deemed the most viable pathway to preserve equitable access within a publicly supported national healthcare system (5, 6).

Additionally, Uruguay possesses a solid baseline infrastructure to support this challenge. The nation has a robust pre-existing experience in hematopoietic stem cell transplantation (HSCT), apheresis, advanced cell processing, and highly specialized supportive care (7). This included immediate, prompt access to a referral pediatric intensive care unit, creating an ideal foundation to mobilize institutional resources and advocacy (8).

Prior to this initiative, CAR T-cell therapy was unavailable within Uruguay. Only one Uruguayan pediatric patient had ever received this advanced therapeutic modality after being referred to an international center abroad. Mirroring the difficult scenario described in Brazil, access for this patient required judicial litigation, bureaucratic delays, and private fundraising campaigns to cover the costs of overseas treatment (1).

The Uruguayan strategy differs fundamentally from the Brazilian experience. In Brazil, the development of CAR T-cell infrastructure has primarily followed a top-down model, promoted by national authorities and major international collaborations (1).

In contrast, Uruguay’s small geographic scale and centralized pediatric care framework allowed for an effective, bottom-up approach. The clinical need was identified directly by pediatric oncologists and patient advocates on the front lines, which successfully mobilized charitable funding to support an autonomous POC manufacturing strategy.

This system utilizes the automated cliniMACS Prodigy® platform, which was established inside a certified Good Manufacturing Practice (GMP) facility located directly within the FPS premises. The product consists of second –generation anti CD19 CAR T- cells generated using a Miltenyi lentiviral vector and incorporating a 4-1BB costimulatory domain. Notably, our facility was built from fundraising without direct initial funding from national authorities. Comprehensive technical transfer and the training of clinical and laboratory personnel were secured through academic collaboration at Hospital Sant Joan de Déu and Hospital Clinic in Barcelona.

Clinical outcomes and early experience

The Uruguayan program was 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 official regulatory offices. Therapy is provided at no cost to affected families, completely independent of their public or private health insurance status, ensuring effective equitable access.

Between August 2025 and May 2026, 5 patients were treated: 4 pediatric patients and 1 young adult who experienced a relapse of ALL originally diagnosed during adolescence. Diagnoses included ALL (n=4) and non-Hodgkin lymphoma (NHL = 1). All patients received a standardized lymphodepletion regimen consisting of cyclophosphamide and fludarabine, followed by the infusion of non-cryopreserved, fresh CAR T-cells at a target dose of 3x10^6/cells/kg.

In terms of safety, severe toxicities occurred but were predictable and manageable (9). Four patients developed Grade 3 cytokine release syndrome (CRS), requiring the administration of tocilizumab and temporary admission to the Pediatric Intensive Care Unit. Three patients developed Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Toxicities resolved in all cases without residual neurological or systemic sequelae.

At the time of this report, all 5 patients remain in complete clinical remission and are measurable residual disease (MRD)-negative as assessed by flow cytometry, showing persistent B-cell aplasia. These clinical outcomes should be interpreted as preliminary, given the small sample size and the short duration of follow-up.

Furthermore, by utilizing fresh, non-cryopreserved cellular products manufactured on-site, the program dramatically optimized logistics (10). It achieved a short vein-to-vein time of less than 12 days. This is a logistical advantage over the commercial timelines which still average 100 to 150 days due to international transport and cryopreservation steps (1).

Discussion and systemic challenges

The high centralization of pediatric cancer care into a single institutional facility, immediate access to specialized intensive care units, effective universal access to medical care, and a favorable national geography eliminate the logistical bottlenecks of long-distance cell transportation. This infrastructure allows prompt, seamless referral to a single manufacturing center.

These favorable conditions-small patient volume, short travel distance, and a single centralized referral center-limit the direct generalizability of this model to larger or more geographically dispersed healthcare systems, where similar PCO strategies would require a substantially different logistical and financial framework.

Nevertheless, translating this scientific innovation into clinical practice was significantly slower than originally anticipated. Although the program was conceived in 2021, the first patient was infused in 2025. This delay was caused by barriers very similar to those faced by Brazil (1): bureaucratic hurdles in specialized equipment importation, lengthy national regulatory approvals for cell therapy products, complex global vector procurement, and the meticulous validation required for a local GMP facility operating under strict international standards.

Maintaining a decentralized POC manufacturing framework demands an incredibly robust, continuous quality management system to ensure compliance with both international cellular therapy standards and evolving local regulations (5).

Scalability also presents a concern. While our current manufacturing capacity covers the national pediatric demand, expanding to adult indications or other hematological malignancies will introduce substantial challenges.

Furthermore, the entire operational model is dependent on imported specialized reagents, disposables, and viral vectors, leaving it exposed to global market bottlenecks and customs delays. Finally, formal long-term financial sustainability has not yet been achieved. Mechanisms for reimbursement from national authorities are still under negotiation.

Conclusion

The Uruguayan experience demonstrates that a public-private and charitable partnership can successfully implement an efficient, pediatric, academic POC CAR T-cell program in Latin America.

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Footnotes

Edited by: Francesco Manfredi, University Hospital Zürich, Switzerland

Reviewed by: Hema Hotchandani, SUNY Upstate Medical University, United States