Automated clinical grade expansion of regulatory T cells in a closed system

Nine years after the first in man report, there are currently close to 30 recruiting or ongoing clinical trials administering Treg in autoimmune diseases, solid organ transplantation, pro-inflammatory diseases and graft-versus-host disease. Given the low frequency of Treg in the periphery, most clinical applications require ex vivo expansion, classifying them as advanced therapy medicinal products (ATMP). Feasibility of good manufacturing practice (GMP) compliant Treg isolation and culture has been proven by several investigators. However, three challenges have to be overcome to make expanded Treg an attractive seminal product for phase III studies and potential market launch. First, other than the vast majority of current expansion protocols, media and cytokine feeds, cell activation, optional transduction and quality control steps should avoid open handling to ensure product and personnel safety. Second, hands-on labor should ideally be minimized to standardize manufacturing, reduce overtime work and thus manufacturing costs. Finally, realization of individualized cellular therapy for large patient cohorts will only be feasible if we can use automated closed manufacturing systems with small footprint.