Enriching central memory T cells using novel bioreactor design for T cell manufacturing

Abstract

The manufacturing of T cell therapies aims to achieve high yields of product with potent phenotypes. We have developed a novel bioreactor, Bioreactor with an Expandable Culture Area – Dual Chamber (BECA-D), which has previously demonstrated functionality for scaled T cell manufacturing. In this study, incorporation of a stirring mechanism into the double-chamber bioreactor design was tested to homogenize the media components between the two chambers. In addition to the improved media homogenization, the stirring culture was also observed to have higher yield and enrichment of central memory T cells, a T cell subpopulation that has been associated with improved therapeutic efficacy, as compared to a static control. BECA-D with a stirring mechanism (BECA-DS+), was evaluated for its performance in culturing T cells in comparison to a static control, BECA-D, and an industry benchmark, G-Rex10. BECA-DS+ was able to preferentially promote the enrichment of central memory T cells compared to the static cultures, indicative of the effect of the stirring mechanism. By achieving high T cell yields with a favorable subpopulation profile, the mechanical method of incorporating stirring into a double-chamber bioreactor such as BECA-D carries great potential as a useful research and manufacturing tool to support advanced T cell therapy manufacturing.