Development of an automated manufacturing process for large-scale production of autologous T cell therapies

Natalie Francis; Marion Braun; Sarah Neagle; Sabine Peiffer; Alexander Bohn; Alexander Rosenthal; Tanita Olbrich; Sophia Lollies; Keijo Ilsmann; Carola Hauck; Bernhard Gerstmayer; Silvio Weber; Aileen Kirkpatrick

doi:10.1016/j.omtm.2023.101114

Development of an automated manufacturing process for large-scale production of autologous T cell therapies

Mol Ther Methods Clin Dev. 2023 Sep 16:31:101114. doi: 10.1016/j.omtm.2023.101114. eCollection 2023 Dec 14.

Affiliations

¹ Cell & Gene Therapy, GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
² Cellular Therapy, Industrial Workflow Development, Miltenyi Biotec B.V. & Co. KG, Friedrich-Ebert-Str. 68, 51429 Bergisch Gladbach, Germany.

Abstract

Engineered T cell therapies have shown significant clinical success. However, current manufacturing capabilities present a challenge in bringing these therapies to patients. Furthermore, the cost of development and manufacturing is still extremely high due to complexity of the manufacturing process. Increased automation can improve quality and reproducibility while reducing costs through minimizing hands-on operator time, allowing parallel manufacture of multiple products, and reducing the complexity of technology transfer. In this article, we describe the results of a strategic alliance between GSK and Miltenyi Biotec to develop a closed, automated manufacturing process using the CliniMACS Prodigy for autologous T cell therapy products that can deliver a high number of cells suitable for treating solid tumor indications and compatible with cryopreserved apheresis and drug product. We demonstrate the ability of the T cell Transduction - Large Scale process to deliver a significantly higher cell number than the existing process, achieving 1.5 × 10¹⁰ cells after 12 days of expansion, without affecting other product attributes. We demonstrate successful technology transfer of this robust process into three manufacturing facilities.

Keywords: CliniMACS Prodigy; GMP; T cell therapy; automation; cell and gene therapy; cell therapy; gene therapy; manufacturing; oncology; technology transfer.