ESTABLISHING A NATIONAL CD19 CAR-T MANUFACTURING PLATFORM IN BRAZIL: TOWARD CLINICAL TRANSLATION FOR PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA

@article{godoy2026establishing,
  title = {{ESTABLISHING A NATIONAL CD19 CAR-T MANUFACTURING PLATFORM IN BRAZIL: TOWARD CLINICAL TRANSLATION FOR PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA}},
  author = {Daniela GODOY and Livia DOURADO and Sabrina REIS and Arthur NEUMANN and Ana Leticia GUTIERREZ and Luiza ABDO and Emmanuel ARAGÃO and Flavio BRAGA and Stephan GRUPP and Stephan KADAUKE and Martín BONAMINO},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.106864},
  url = {https://doi.org/10.1016/j.htct.2026.106864},
  note = {CC BY},
}

TY  - JOUR
TI  - ESTABLISHING A NATIONAL CD19 CAR-T MANUFACTURING PLATFORM IN BRAZIL: TOWARD CLINICAL TRANSLATION FOR PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA
AU  - Daniela GODOY
AU  - Livia DOURADO
AU  - Sabrina REIS
AU  - Arthur NEUMANN
AU  - Ana Leticia GUTIERREZ
AU  - Luiza ABDO
AU  - Emmanuel ARAGÃO
AU  - Flavio BRAGA
AU  - Stephan GRUPP
AU  - Stephan KADAUKE
AU  - Martín BONAMINO
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.106864
UR  - https://doi.org/10.1016/j.htct.2026.106864
AB  - Introduction: Limited access to commercially available chimeric antigen receptor T-cell (CAR-T) therapies remains a major challenge for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia in Brazil. Through a technology transfer from the Children's Hospital of Philadelphia (CHOP), the Brazilian National Cancer Institute (INCA) is establishing an institutional platform for manufacturing autologous CD19-directed CAR-T cells, creating the foundation for sustainable national production and an investigator-initiated clinical trial. Objectives: To describe the implementation of the CAR-T manufacturing platform at INCA and the coordinated activities supporting clinical translation, including technology transfer, manufacturing training, product quality assessment, GMP infrastructure implementation, regulatory progress, and clinical team preparation. Materials and methods: Two manufacturing training runs were performed using leukapheresis-derived peripheral blood mononuclear cells processed on the closed, semi-automated CliniMACS Prodigy platform. T cells were enriched, activated, lentivirally transduced with an anti-CD19 CAR construct, expanded, harvested, and cryopreserved. Final products were evaluated according to predefined release criteria, including cell identity, viability, transduction efficiency, residual B cells, sterility, endotoxin, mycoplasma, vector copy number (VCN), and replication-competent lentivirus (RCL). In parallel, a manufacturing facility dedicated to Advanced Therapy Medicinal Products was designed in compliance with Good Manufacturing Practices (GMP) for sterile medicinal products and Brazilian regulatory requirements. Manufacturing and clinical teams completed structured technology transfer and specialized training. Results: Both training runs successfully met all predefined product quality criteria, demonstrating reproducible implementation of the transferred manufacturing process. Cell viability reached 91% and 95%, CD3+ cells represented 88% and 89%, and CAR expression was 37% and 27% in runs 1 and 2, respectively. Residual CD19+/CD20+ cells ranged from 0.00% to 0.01%. Endotoxin levels remained below 0.250 EU/mL, sterility testing showed no microbial growth after 14 days, mycoplasma and replication-competent lentivirus were not detected, and VCN values were 2.6 and 2.0 copies per transduced cell. The first training run yielded 1.8 × 10⁹ cells after six days of expansion. Additionally, the GMP facility design received approval from the Brazilian Health Regulatory Agency (Anvisa), the clinical protocol is currently under review by CEP/CONEP, and the multidisciplinary clinical team completed specialized training at CHOP for CAR-T patient management. Conclusions: The coordinated implementation of manufacturing capabilities, product quality assessment, GMP-compliant infrastructure, regulatory advancement, and multidisciplinary training demonstrates substantial institutional readiness for clinical translation of CAR-T therapy at INCA. Beyond supporting the planned initiation of the institutional pediatric CD19 CAR-T clinical trial in 2027, these achievements establish a national manufacturing platform capable of expanding equitable access to advanced cellular therapies within the Brazilian Unified Health System.
SN  - 2531-1379
SN  - 2531-1387
ER  -