Perfusion microbioreactor for CAR-Treg manufacturing

TL;DR

A new compact microbioreactor improves the efficiency and scalability of manufacturing CAR-Treg cell therapies.

Contribution

A closed microbioreactor platform (K-MBR) is developed for efficient, decentralized cell therapy manufacturing.

Findings

The K-MBR achieves 92% higher yield of CAR-Tregs compared to conventional methods.

Spatial confinement increases lentiviral transduction efficiency in primary human cells.

The platform reduces the physical footprint of cell manufacturing and supports automation.

Abstract

Manufacturing cell and gene therapies (CGTs) at scale presents challenges in cost, product consistency, and adaptability to personalized treatments. Traditional large-volume bioreactors are designed to support cell growth through controlled nutrient delivery and gas exchange, but are poorly suited to the decentralized, small-batch production required for personalized therapies such as chimeric antigen receptor (CAR) T cells. To address this, we have developed the KCL-Microbioreactor (K-MBR), a closed microbioreactor platform based on microfluidic principles. Engineered in polydimethylsiloxane (PDMS), the K-MBR combines spatial confinement, semi-continuous perfusion, and integrated viral transduction in a compact footprint, enabling efficient gene delivery and robust expansion of therapeutic cells. We demonstrate the platform’s utility by generating functional CAR-Tregs targeting HLA-A2, achieving a 92% increase in yield compared to conventional methods. The K-MBR offers a streamlined solution for CGT manufacturing, with potential to reduce production costs and enhance scalability across a broad range of cell therapies.

•Perfusion microbioreactor achieves Treg expansion comparable to gold standard G-Rex device•Spatial confinement increases lentiviral transduction efficiency of primary human cells•Compact, low-volume platform reduces the physical footprint of cell manufacturing•Device supports future automation and advances progress toward point-of-care production

Perfusion microbioreactor achieves Treg expansion comparable to gold standard G-Rex device

Spatial confinement increases lentiviral transduction efficiency of primary human cells

Compact, low-volume platform reduces the physical footprint of cell manufacturing

Device supports future automation and advances progress toward point-of-care production

Biological sciences

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