Large-scale expansion and characterization of CD3+ T-cells in the Quantum® Cell Expansion System

• Main Authors: Claire Coeshott, Boah Vang, Mark Jones, Brian Nankervis
• Format: Article
• Language: English
• Published: BMC 2019-08-01
• Series: Journal of Translational Medicine
• Subjects: Cell expansion; Cell proliferation; Hollow-fiber; Immunotherapy; Quantum; T-cell
• Online Access: http://link.springer.com/article/10.1186/s12967-019-2001-5

Abstract Background The rapid evolution of cell-based immunotherapies such as chimeric antigen receptor T-cells for treatment of hematological cancers has precipitated the need for a platform to expand these cells ex vivo in a safe, efficient, and reproducible manner. In the Quantum® Cell Expansion System (Quantum system) we evaluated the expansion of T-cells from healthy donors in a functionally-closed environment that reduces time and resources needed to produce a therapeutic dose. Methods Mononuclear cells from leukapheresis products from 5 healthy donors were activated with anti-CD3/CD28 Dynabeads® and expanded in the Quantum system for 8–9 days using xeno-free, serum-free medium and IL-2. Harvested cells were phenotyped by flow cytometry and evaluated for cytokine secretion by multiplex assays. Results From starting products of 30 or 85 × 106 mononuclear cells, CD3+ T-cell populations expanded over 500-fold following stimulation to provide yields up to 25 × 109 cells within 8 days. T-cell yields from all donors were similar in terms of harvest numbers, viability and doubling times. Functionality (secretion of IFN-γ, IL-2 and TNF-α) was retained in harvested T-cells upon restimulation in vitro and T-cells displayed therapeutically-relevant less-differentiated phenotypes of naïve and central memory T-cells, with low expression of exhaustion markers LAG-3 and PD-1. Conclusions The Quantum system has been successfully used to produce large quantities of functional T-cells at clinical dosing scale and within a short timeframe. This platform could have wide applicability for autologous and allogeneic cellular immunotherapies for the treatment of cancer.