Streamlining CAR T Cell Manufacturing: Automated CD19 CAR-T Production Using the Cocoon® Platform in a Phase 2 Clinical Trial

Due to global unmet patient need for CAR T cell therapies, there is growing demand for scalable, cost-effective, and simplified CAR-T manufacturing. We evaluated the feasibility of manufacturing CD19 CAR T cells using the Lonza Cocoon® Platform, an automated bioreactor system, and compared it to an established manual process.

In a clinical trial for CD19+ malignancies, seven patient products successfully meeting all release criteria were manufactured using the Cocoon® Platform. Over a 10-day process, the Cocoon® Platform-derived CAR T cells achieved an average of 85-fold expansion (range: 25–142), yielding 2.1×10⁹ cells (range: 1.2–2.7×10⁹) post-harvest. Transduction efficiency averaged 37% (range: 18–73%) which is the ideal range to ensure vector copy number meets specification (<5 copies/transduced cell). By comparison, six parallel products manufactured manually using a G-Rex® and RetroNectin® coated plates produced an average fold expansion of 69-fold (range 18-98), an average yield of 2.0x109 cells (range 1.1-2.8x109 cells), and 76% average transduction efficiency (range 73-80%).

Despite different transduction methods, the Cocoon® Platform delivered comparable results to the manual method and met the required dose levels. With the Cocoon® Platform, we reduced cleanroom entries (5 vs. 8 in the manual process) and hands-on time (9 vs. 13 hours). Material costs for both methods remained below published benchmarks. [JE1] Looking ahead, Cocoon® manufacturing offers the opportunity to transition manufacturing into a Grade C/ISO8 environment, enabling further cost reductions and improved throughput.

The automated Lonza Cocoon® Platform simplifies CAR T cell manufacturing, potentially expanding access to personalized treatments.