可控激活调控搅拌罐生物反应器中的 T 细胞扩增与表型

By tailoring the stirring profile of STBs (Ambr 15 bioreactors; Sartorius, G ttingen, Germany), microbeads functionalized with anti-CD3/CD28 antibodies allow control over the initiation/termination of T-cell activation without requiring additional washing steps to remove the activation signaling cues.

This strategy resulted in up to a 10-fold increase in T-cell numbers compared with conventional static culture systems, resulting in a final cell concentration of 2.5 10 7 cells/mL after 10 days of culture. Importantly, a higher proportion of CD8 + T cells and lower expression of exhaustion markers programmed cell death protein 1, lymphocyte activation gene 3 and T-cell immunoglobulin and mucin domain 3 (<8%) were obtained in STBs relative to static cultures. Additionally, the anti-CD3/CD28-functionalized microbeads were as efficient as the standard TransAct (Miltenyi Biotec, Bergisch Gladbach, Germany) stimuli in activating and expanding T cells in STBs.

Overall, this approach presents a promising strategy for the scalable and tightly controlled manufacturing of T-cell therapies, particularly focusing on the T-cell activation step while minimizing manual operations, thus contributing towards more effective and cost-efficient immunotherapies.