# 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.

## Key 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