Samuel C F Couto, PhD
Laboratory Coordinator
Fundação Pró-Sangue (Blood Center of São Paulo)/University of São Paulo
São Paulo, Brazil
Co-Chair: Lilia Carolina León-Moreno, PhD., Centro de Investigación y Asistencia en Tecnologia y Diseño del Estado de Jalisco, Mexico
Panelists:
Virgínia Picanço e Castro, PhD, Ribeirão Preto Blood Center, Brazil
Andrés Goméz-De Leon, MD, Universidad Autónoma de Nuevo León, Mexico
Chase D. McCann, PhD, MSPH, Children’s National Hospital, USA
The ISCT South & Central America (SCA) Regional Executive Committee and the Early Stage Professional SCA Subcommittee recently hosted a webinar titled "Navigating CAR-T Cell Therapy Development: Insights from Leading SCA Academic Centers." This engaging session brought together esteemed speakers who shared their regional experiences, challenges, and innovations in CAR-T therapy. The progress in SCA has been steady, with the region emerging as a key player in the global market. This growth is supported by constant regulatory reforms, clinical advancements, and a rising interest in biotechnology. However, unlocking the full potential of these cutting-edge therapies in this region requires overcoming challenges such as gaps in infrastructure, regulatory frameworks, and public awareness.
Dr. Virginia Picanço opened the session by chronicling Brazil’s remarkable journey in CAR-T cell therapy, focusing on the milestones achieved by the Blood Center of Ribeirão Preto. She traced the origins of the project, which began with preclinical studies in 2015 and culminated in the treatment of the first patient in 2019. As an academic center affiliated with the University of São Paulo, the facility has played a pivotal role in developing and optimizing CAR-T manufacturing processes. An interesting point was the center’s transition from an open-system manufacturing process using flask cultures to a more sophisticated closed-system using culture bags. To address the initial challenges of importing lentiviral vectors, the team designed and validated their own vectors, laying the groundwork for scalable, high-quality production. She also highlighted the establishment of NUTERA, a state-of-the-art facility supported by federal and state governments, designed to meet GMP standards and provide CAR-T therapies to patients within Brazil’s public health system. One of the critical aspects of Dr. Picanço’s presentation was the emphasis on building a robust quality management system, which now oversees every step of the manufacturing process. With over 800 approved documents, extensive personnel training, and ongoing process validations, the center has demonstrated a commitment to producing safe and effective therapies. Dr. Picanço also unveiled exciting future plans, including the development of CAR-NK cells, an allogeneic approach that could address some of the limitations of current CAR-T therapies such as CRS and donor compatibility.
Dr. Andrés Goméz presented a sobering yet inspiring account of the hurdles faced by Mexico in implementing CAR-T cell therapies. With limited regulatory frameworks and infrastructural challenges, the path to accessible CAR-T treatments has been fraught with obstacles. Dr. Goméz highlighted the stark reality of uneven access to stem cell transplantation across the region, noting that while Mexico ranks among the top three countries in South and Central America for such procedures, the lack of regulations for advanced therapies has hindered progress. Despite these challenges, Dr. Goméz and his team adopted a decentralized, point-of-care manufacturing approach. Utilizing the CliniMACS Prodigy system for automated CAR-T cell production, they successfully navigated the complexities of regulatory approval, including obtaining Mexico’s first viral vector import permit. He shared the team’s struggles with regulatory agencies, recounting miscommunications that delayed critical advancements, such as instances where CD19 was mistaken for COVID-19. Nonetheless, the team persevered, securing the necessary permits and laying the foundation for Mexico’s first clinical trial involving CAR-T cells for CD19-positive acute lymphoblastic leukemia patients. Dr. Goméz emphasized the importance of regional collaboration, citing initiatives like the CARLA academic consortium, which fosters knowledge-sharing among Latin American countries. His presentation underscored the urgent need for regulatory reform, local capacity building, and collaborative efforts to make CAR-T therapies more accessible and affordable in Mexico and beyond.
Dr. Chase McCann offered a forward-looking perspective on the development of CAR-T therapies for pediatric cancers. Dr. McCann highlighted the innovative work being done at the Children’s National Hospital (CNH) in Washington, D.C., an academic pediatric center that has emerged as a leader in cell and gene therapy research. With two state-of-the-art manufacturing cleanrooms and extensive experience in producing over 600 cell therapy products, CNH has focused on developing therapies tailored to the needs of pediatric patients. One of the most promising initiatives he discussed was the NexTGen Cell Therapies for Childhood Cancers project. This international collaboration unites experts from Children’s National Hospital, University College London, and the Dana-Farber Cancer Institute, among others. The initiative, supported by Cancer Grand Challenges through the UK Cancer Research Council and the U.S. National Institutes of Health (NIH), is designed to address the unmet medical needs of pediatric patients with innovative therapeutic approaches. The NexTGen team’s multi-faceted strategy to revolutionize pediatric cancer treatments is based on the combination of tumor-associated antigen T (TAA-T) cells and B7H3 CAR-T cells. TAA-T cells target a spectrum of tumor-associated antigens, providing clonal diversity and reducing the risk of tumor antigen escape. When paired with B7H3 CAR-T cells—engineered to recognize and attack the B7H3 immune checkpoint molecule commonly expressed in pediatric cancers like Ewing sarcoma, osteosarcoma, and medulloblastoma—this combination has demonstrated synergistic tumor-killing effects in preclinical studies. To further enhance the functionality of these therapies within the TME, the NexTGen team is incorporating a dominant-negative TGF-beta receptor into their engineered T cells. This modification helps counteract the immunosuppressive signals typically present in the tumor microenvironment, thereby boosting T-cell activity and persistence. The NexTGen team is also pioneering innovative study designs to optimize the development and evaluation of these therapies. Their clinical trials compare two distinct cell therapy products across three academic sites and different patient populations, providing a robust framework for assessing efficacy and safety. This approach not only accelerates the development process but also establishes a blueprint for future multicenter trials in pediatric oncology. Dr. McCann emphasized that while academic centers like CNH are leading the charge in innovation, the transition from early-phase trials to widespread clinical application requires substantial support from industry. Without such partnerships, many of these groundbreaking therapies risk becoming stuck in what is known as “valley of death,” where promising treatments fail to progress beyond Phase I trials. He applauded initiatives like the Pediatric Advanced Medicine Biotech (PAMB), which brings together academia, industry, and regulatory bodies to foster collaboration and ensure these therapies reach the patients who need them most.
The webinar provided an enlightening exploration of the innovative approaches, challenges, and opportunities in CAR-T therapy development across South and Central America. Each presentation demonstrated the resilience and ingenuity of academic centers in overcoming barriers unique to their contexts. These efforts not only advance the science of CAR-T therapies but also emphasize the importance of collaboration—between academia, industry, and regulatory bodies—to bridge gaps in access and affordability. The collective commitment to addressing regional disparities and driving innovation offers hope for a future where life-saving therapies are within reach of every patient who needs them. As we look ahead, these discussions serve as a powerful reminder of the transformative potential of partnership and persistence in shaping the next chapter of cell and gene therapy.
References
- Picanço-Castro V, Moço PD, Mizukami A, Vaz LD, de Souza Fernandes Pereira M, Silvestre RN, de Azevedo JTC, de Sousa Bomfim A, de Abreu Neto MS, Malmegrim KCR, Swiech K, Covas DT. Establishment of a simple and efficient platform for car-t cell generation and expansion: from lentiviral production to in vivo studies. Hematol Transfus Cell Ther. 2020 Apr-Jun;42(2):150-158. doi: 10.1016/j.htct.2019.06.007. Epub 2019 Oct 9. PMID: 31676276; PMCID: PMC7248496.).
- Donadel, C.D., De Santis, G.C., Gonçalves, T.E. et al. Safety and efficacy of a new academic CD19-directed CAR-T cell for refractory/relapsed non-Hodgkin lymphoma and acute lymphoblastic leukemia in Brazil. Bone Marrow Transplant 59, 1040–1042 (2024). https://doi.org/10.1038/s41409-024-02283-6
- Chávez-Estrada, R. Salazar-Riojas, D.M. Alvarado-Navarro, A.K. Hernández-Navarro, M.B. Ake-Uc, N.K. Moncada-Saucedo, A. Gómez-De León, P. Colunga-Pedraza, V. Jiménez-Antolínez, C. Gutierrez-Aguirre, O. Cantu-Rodriguez, F. Künkel, D. Gómez-Almaguer, Immunophenotypic Characterization of the first CD19+ CAR-T Cells In Mexico, Cytotherapy, Volume 26, Issue 6, Supplement, Page S159, 2024. ISSN 1465-3249, https://doi.org/10.1016/j.jcyt.2024.03.310.
- Amy B. Hont et al., Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. JCO 37, 2349-2359, (2019). DOI:10.1200/JCO.19.00177
- Mackall, C.L., Bollard, C.M., Goodman, N. et al. Enhancing pediatric access to cell and gene therapies. Nat Med 30, 1836–1846 (2024). https://doi.org/10.1038/s41591-024-03035-1
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