Continuous Perfusion at Dose-Scale for Cell Therapy Process Development

With several CAR-T cell immunotherapy products currently marketed for the treatment of hematological cancers, there are increasing efforts to develop better technologies and processes for cell therapies to improve efficacy, reduce variability, and decrease costs. Ways to optimize cell activation, transduction, and expansion for cell-based treatments are improving, but major challenges still exist in experiment reproducibility and robustness during process development. Variability of donor and patient-derived material can confound experiment results. Reagent cost, scarce bench space, and busy scientists can limit the number of experiments possible. Therefore, process development experiments are typically done in milliliter-sized static plates with minimal environmental control and can lead to sub-optimal outcomes.

To address this gap, we investigated a perfusion microbioreactor (Breez™) that can support >400M cells in only a 2mL working volume. This fully closed single-use perfusion bioreactor operates outside of a biosafety cabinet and replicates bench scale perfusion processes at industrially relevant cell densities. The use of integrated microfluidics reduces labor, bench space, and materials, enabling a single donor to be used in many bioreactor experiments.

This is a recorded version of an in-person presentation for CAR-TCR Summit 2022.