In a significant leap forward for cancer treatment, scientists at the Singapore-MIT Alliance for Research and Technology have introduced a revolutionary microfluidic chip that promises to transform the production of CAR T-cells. This new technology, a compact automated system roughly the size of a pack of cards, enables the production of clinical doses of autologous chimeric antigen receptor CAR T-cells with remarkable efficiency. By minimizing the size and resource requirements compared to existing manufacturing platforms, this innovation could make cell therapies more affordable and accessible.
CAR T-cell therapy involves extracting a patient’s own T-cells, genetically modifying them to target cancer cells, and then expanding these modified cells before reinfusing them into the patient. Despite its success in treating certain cancers, the traditional production of CAR T-cells is plagued by high costs, lengthy production times, and a risk of contamination. The new SMART-developed system, detailed in their recent paper published in Nature Biomedical Engineering, addresses these issues by utilizing a microbioreactor that can process T-cells in a much smaller and more controlled environment.
The new method allows for the activation, transduction, and expansion of human primary T-cells within a 2-milliliter microfluidic chip. This system has demonstrated the capability to produce over 60 million CAR T-cells from donors with lymphoma and more than 200 million from healthy donors, all within a significantly smaller footprint. The efficiency of this system reduces the cost of goods manufactured, which could lead to lower patient costs for CAR T-cell therapies.
The research team, including Michael Birnbaum, Wei-Xiang Sin, and Narendra Suhas Jagannathan, alongside collaborators from institutions such as Duke-NUS Medical School and Singapore General Hospital, have highlighted the potential of this microfluidic chip to support point-of-care manufacturing. This could make it feasible to produce CAR T-cells directly in hospitals or clinics, potentially reducing production times from 12 days to as little as seven or eight days, and thereby cutting down the wait time for patients.
The microbioreactor’s design incorporates a closed system that minimizes contamination risk and maximizes process control. Its compact size means that it requires less medium and fewer reagents compared to larger systems. This not only decreases the cost associated with reagents and materials but also makes it possible to use the technology with smaller initial cell numbers. Such a capability is particularly beneficial for pediatric patients or those with limited T-cell quantities.
Moreover, the SMART team’s innovation allows for high-density T-cell expansion with minimal space and resources, paving the way for future advancements in decentralized CAR T-cell production. The researchers plan to further refine the system to enhance cell yield and quality, potentially leading to even greater improvements in the accessibility and effectiveness of cell therapies.
The development of this miniaturized microbioreactor represents a major advancement in cell therapy manufacturing, addressing some of the most pressing challenges in the field. With support from the National Research Foundation Singapore under its Campus for Research Excellence and Technological Enterprise program, this breakthrough could set a new standard for the production of life-saving therapies and bring CAR T-cell treatment closer to patients in need.
