Abstract:
Autologous cell-based therapeutics have gained increasing attention in recent years because of their efficacy at treating diseases with limited therapeutic options. Chimeric antigen receptor (CAR) T-cell therapy has demonstrated clinical success in hematologic oncology indications, providing critically ill patients with a potentially curative therapy. Although engineered cell therapies such as CAR T cells provide new options for patients with unmet needs, the high cost and complexity of manufacturing may hinder clinical and commercial translation. The Cocoon® Platform (Lonza, Basel, Switzerland) addresses many challenges, such as high labor demand, process consistency, contamination risks and scalability, by enabling efficient, functionally closed and automated production, whether at clinical or commercial scale. This platform is customizable and easy to use and requires minimal operator interaction, thereby decreasing process variability. We present two processes that demonstrate the Cocoon® Platform's capabilities. We employed different T-cell activation methods—OKT3 and CD3/CD28 Dynabeads (Thermo Fisher Scientific, Waltham, MA, USA)—to generate final cellular products that meet the critical quality attributes of a clinical autologous CAR T-cell product. This study demonstrates a manufacturing solution for addressing challenges with manual methods of production and facilitating the scale-up of autologous cell therapy.
Authors: Nuala Trainor, Kelly A. Purpura, Kevin Middleton, Karen Fargo, Lauren Hails, Michele Vicentini-Hogan, Chase McRobie, Raelyn Daniels, Phil Densham, Paul Gardin, Michael Fouks, Hadar Brayer, Rivka Gal Malka, Anastasia Rodin, Tal Ogen, Michal J. Besser, Tim Smith, David Leonard, and Adam Bryan