Automated production of gene-modified chimeric antigen receptor T cells using the Cocoon Platform.

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.

Synthesis and characterization of single-phase silicon-substituted alpha-tricalcium phosphate.

Silicon-substituted calcium phosphate (CaP) powders with a Ca/(P+Si) ratio of 1.50 have been prepared by a wet chemical method, with silicon contents up to 2.16 weight percent (wt%). Sintering for 2 h at 1250 degrees C yields single-phase silicon-substituted alpha tricalcium phosphate (Si-alpha-TCP) for compositions between 0.59 and 1.14 wt% silicon. The sintered powders have been characterized with X-ray fluorescence (XRF) spectrometry, X-ray diffraction (XRD), attenuated total reflection infrared spectroscopy (ATR-IR) and transmission electron microscopy (TEM). Compositions with less than 0.59 wt% silicon result in mixtures of Si-alpha-TCP, beta-TCP, and calcium hydroxyapatite (HA), while compositions with more than 1.14 wt% silicon result in mixtures of Si-alpha-TCP and HA. The lattice parameters of single-phase Si-alpha-TCP prepared with 0.87 wt% silicon are a=12.874(1)A, b = 27.372(2) A, c = 15.225(1) A, and beta = 126.38(1) degrees .