Overcoming access barriers in European CAR-T therapy: the role of decentralized manufacturing and the EASYGEN framework.

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapies have revolutionized the treatment of refractory B-cell malignancies, with seven approved therapies in major jurisdictions and rapid label expansion toward earlier lines of treatment. Nevertheless, patient access remains limited by multiple bottlenecks, including shortages of lentiviral vectors, manufacturing capacity constraints, and economic factors, such as prolonged production timelines, high treatment costs and associated reimbursement challenges, and long travel distances for patients to specialized CAR-T treatment centers. Recent advances in nonviral gene delivery, automated bioprocessing, and in vivo T-cell engineering promise to compress production timelines and reduce costs, thereby enabling broader indications, including solid cancers and autoimmune diseases.

METHODS: This review provides an overview of autologous manufacturing and delivery bottlenecks across Europe, outlines rapid manufacturing technologies and decentralized production models, and analyzes the regulatory and scientific frameworks that govern the implementation of advanced therapy medicinal products (ATMPs). In addition, it surveys nonviral and in vivo CAR-T therapy approaches and summarizes the contributions of pan-European consortia dedicated to harmonizing clinical translation, automation, and real-world data integration.

RESULTS: The EASYGEN "EASY workflow integration for GENe therapy" consortium (Grant-ID: 101194710), funded under the Innovative Health Initiative (IHI) Call 7.2 ("User-centric technologies and optimized hospital workflows for a sustainable healthcare workforce"), aims to operationalize these advances by building a modular platform for CAR-T and gene-modified immune-cell manufacturing. EASYGEN unites industrial, clinical, and academic partners to propose a scalable, decentralized point-of-care CAR-T manufacturing solution, implementing next-generation technologies such as nonviral gene transfer at the point-of-care (PoC) with interoperable data standards across multiple European sites. The consortium aims to provide a blueprint for equitable advanced therapy production and regulatory integration, while also easing hospital workflows and reducing the burden on healthcare staff by minimizing administrative complexity and coordinating inclusive data harmonization efforts within hospitals.

CONCLUSIONS: Beyond operational efficiency, the consortium aims to highlight how reduced vein-to-vein time, decentralized production, and improved hospital workflows may translate into fewer patients deteriorating or becoming ineligible during waiting periods.