Access to advanced therapies is often framed as a challenge of resources and infrastructure. But in Europe, a bold new model is reshaping how patients receive life-saving CAR T-cell therapy. Instead of relying solely on commercial manufacturing and centralized approval processes, the Hospital Clínic de Barcelona has pioneered a hospital-based pathway that delivers CAR-T directly within the public health system—bringing cutting-edge treatments closer to patients who need them most.
September’s Bridging the Gap webinar, “Decentralizing CAR-T in Europe: Inside and Beyond Hospital Clínic de Barcelona’s ARI Program,” featured Dr. Manel Juan Otero, Head of the Immunology Department at Hospital Clínic de Barcelona, and Sergio Navarro Velázquez, Co-Manager of the Immunology Department. They shared how Spain’s ARI program is transforming access to CAR-T therapies while shaping the future of academic innovation across Europe.
The webinar conversation was hosted by Olga Bukatova from Azenta Life Sciences, with insights from George Eastwood, Executive Director of the Emily Whitehead Foundation, and co-host Tom Whitehead of the Emily Whitehead Foundation.
The Hospital Exemption Pathway: A European Model for Access
Dr. Juan described how Spain leverages the European Union’s hospital exemption rule to create treatments within a public hospital setting. Unlike other countries where exemptions are limited, Spain’s system allows academic centers to manufacture therapies once efficacy and safety are demonstrated.
“Our model is based on this centralized concept. We are working in a public hospital, with patients, trying to solve the problems we have here,” Dr. Juan said. “Hospital exemption lets us treat patients step by step, without requiring the kind of large-scale trials that academic centers could never afford.”
This framework has enabled Hospital Clínic de Barcelona to develop two landmark therapies:
- ARI-0001 (Varnimcabtagene Autoleucel), an autologous CAR-T engineered to target CD19 on B cells. Developed entirely in-house, it became Europe’s first fully academic CAR-T and is used to treat relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) as well as certain non-Hodgkin lymphomas.
- ARI-0002h (Cesnicabtagene Autoleucel), a humanized CAR-T therapy that targets BCMA, a key marker in multiple myeloma. By reducing the risk of immune rejection and improving durability, it expands treatment options for patients with relapsed or refractory multiple myeloma.
Together, these programs have already brought treatment to more than 500 patients in Spain’s public healthcare system.
From Bench to Bedside: Clinical Outcomes of ARI-0001 and ARI-0002h
Mr. Navarro outlined the clinical progress of the ARI program. ARI-0001 began with early trials in relapsed/refractory acute lymphoblastic leukemia and expanded to additional B-cell malignancies under compassionate use. ARI-0002h followed, offering a much-needed option for multiple myeloma patients.
“What stands out,” Navarro emphasized, “is that our fractionated infusion approach results in very low rates of cytokine release syndrome and ICANS, compared to commercial CAR-Ts. This allows us to treat safely, directly next to the patient, without losing efficacy.”
Their innovations extend beyond treatment outcomes. By building manufacturing capacity inside the hospital, clinicians can adapt protocols quickly, reduce logistical delays, and avoid shipping patient cells across borders.
Patient Stories Driving Innovation: The Legacy of Arianna Bedele
Behind the ARI program is the remarkable story of Arianna Bedele, a young leukemia patient in Spain whose courage helped inspire the project. Arianna’s journey was chronicled in the documentary The Story of Love and Life, released in Spain in 2022. Though she passed away in 2016, her legacy became the spark for Hospital Clínic de Barcelona’s Project ARI, leading to the development of ARI-0001 and ARI-0002h. These therapies have since reached hundreds of patients through Spain’s public health system.
“When you’re a parent with a sick kid, you’ll give up every material thing you have,” Tom said. “But we need to make follow-up easier and less costly”.
Arianna’s life continues to shape how access and advocacy are framed in Europe, ensuring that the patient voice remains central to innovation.
Harnessing Digital Tools and AI for CAR-T Manufacturing
The Hospital Clínic de Barcelona team is also a leader in digital transformation. Navarro described their role in AIDPATH (Artificial Intelligence Decentralized Production for Advanced Therapies in the Hospital), a European consortium integrating clinical and manufacturing data to create “digital twins” of CAR-T production.
Digital twins are virtual models that mirror real-world processes, allowing researchers to simulate and predict outcomes before applying changes to actual patients or manufacturing systems. For example, these models can help anticipate batch variability or even predict which patients may be at higher risk for cytokine release syndrome, enabling clinicians to intervene earlier.
“This helps us predict not only the quality of our CAR-T products but also patient outcomes,” Navarro explained. “It’s the first step in fully digitalizing our process and improving personalization.”
Eastwood noted the broader potential of AI: “Even synthesizing long regulatory submissions or connecting data across silos is powerful. But in manufacturing especially, what if an insight in one batch could immediately improve the next? That’s where AI could change the game.”
Scaling Decentralized CAR-T Across Europe
Looking to the future, Dr. Juan emphasized that Barcelona’s mission is not to treat every patient in the country, but to share knowledge and enable other centers to replicate the model. Networks are already forming in Spain and the Netherlands to expand hospital-based CAR-T production.
“We want to help anyone who wants to treat their patients,” Dr. Juan said. “Science is based on sharing, and our goal is to provide tools and collaborate so that more patients across Europe—and beyond—can benefit.”
Both speakers highlighted plans to advance ARI-0003, a dual CAR-T combining ARI-0001 and ARI-0002h, and to explore new applications in autoimmune disease and transplantation. “We are in a really new situation,” Navarro concluded. “The opportunity to make things better for patients has never been greater.”
Key Takeaways
- Hospital exemption enables academic CAR-T manufacturing: Spain’s model allows hospitals to treat patients without industry-scale trials, while still ensuring safety and efficacy.
- ARI-0001 and ARI-0002h set new benchmarks: These hospital-developed CAR-Ts target CD19 and BCMA, respectively, offering options for leukemia, lymphoma, and multiple myeloma.
- Fractionated dosing improves safety: ARI-0002h’s unique infusion strategy reduces severe side effects while maintaining strong efficacy.
- AI is entering CAR-T production: Digital twin models and predictive analytics can streamline manufacturing and personalize treatments.
- Collaboration drives scalability: Barcelona is building networks in Spain and abroad to decentralize CAR-T delivery across Europe.
- Next-generation therapies are underway: Dual-target CAR-Ts and trials in autoimmune disease and transplantation represent the next frontier.
Closing Reflections
As Bukatova observed, the ARI program mirrors the spirit of patient-driven innovation that began with Emily Whitehead’s pioneering CAR-T treatment in the United States. By grounding science in patient stories—like Arianna Bedele in Spain—this movement ensures that innovation stays tethered to its true purpose.
Eastwood closed with a reminder: “So much progress happens when we share openly. The ARI program is proof that decentralized, academic-led innovation can transform access. The challenge now is scaling these models worldwide.”
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About the Guests
Manel Juan Otero, M.D., Ph.D.
Head of the Immunology Department, Hospital Clínic de Barcelona
Manel Juan Otero is a Spanish immunologist who has authored over 200 publications, supervised 15 doctoral theses, and holds 9 patents. His research focuses on T cell biology, HLA polymorphisms, and advanced immunotherapies, including CAR-T therapies ARI-0001 and ARI-0002h, which have treated more than 500 patients in Spain’s public health system. He has led 24 competitive projects and achieved an H-index of 57, positioning him among Spain’s leading experts in immunology.
Sergio Navarro Velázquez M.Sc
Co-Manager Immunology Department, Hospital Clínic de Barcelona
Sergio Navarro Velázquez is a Spanish immunologist and biochemist trained in immunology, bioinformatics, and cancer immunotherapy. His work bridges biomedical research and AI, contributing to projects such as AIDPATH, which automates CAR-T cell manufacturing and monitoring. He is pursuing a PhD on the characterization and clinical outcomes of CAR-T ARI-0001 within Dr. Manel Otero’s group and has published several impactful studies as an emerging researcher in CAR-T therapies.