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Researchers from the Singapore-MIT Alliance for Research and Technology (SMART), in collaboration with the Singapore Centre for Environmental Life Sciences Engineering (SCELSE) and the Massachusetts Institute of Technology (MIT), have developed a new method to rapidly detect contaminants in T-cell cultures. This technique, which combines advanced long-read nanopore sequencing with machine learning, promises to significantly enhance the safety and efficiency of cell therapy manufacturing.
Revolutionizing Sterility Testing in Cell Therapy
The importance of ensuring microbial safety in cell therapies, such as chimeric antigen receptor T-cells (CAR-T) used in blood-related cancer treatments, cannot be overstated. Traditional sterility testing methods, which are essential for ensuring the safety of these living medicines, typically take between seven to 14 days. The novel method developed by SMART researchers can accomplish this task within 24 hours, a significant improvement that could be critical for patients requiring urgent treatment.
Published in the journal Microbiology Spectrum, the paper titled “Machine learning-based detection of adventitious microbes in T-cell therapy cultures using long-read sequencing” outlines the new method. This approach uses third-generation nanopore long-read sequencing and DNA extraction technologies, along with machine learning algorithms, to quickly and accurately detect and identify microbial contaminants, even those present in low abundance.
The Technology Behind the Advancement
The method involves utilizing nanopore long-read sequencing to identify microorganisms. This is followed by an advanced machine learning algorithm for computational analysis and optimization. This combination allows for the quick identification of both the presence and types of microbial contaminants, surpassing the speed of standard compendial tests.
Dr. James Strutt, Senior Postdoctoral Associate at SMART CAMP and first author of the paper, emphasized the broad practical applications of this discovery. "It offers faster product validation for biopharmaceutical manufacturers, reducing downtime and potentially accelerating product-to-market timelines," he stated. This advancement not only enhances quality control but also improves overall efficiency and cost-effectiveness, ultimately benefiting patients by ensuring the safety and reliability of cell therapy products.
Looking Towards the Future
The research, presented at various international symposiums, is part of SMART CAMP's ongoing efforts to integrate this novel T-cell sterility test into their processes and further refine the accuracy of contamination detection. Future research aims to provide a similar level of detection for viruses, enhancing the robustness of sterility assessments.
Co-corresponding author Dr. Stacy L. Springs, Principal Investigator at SMART CAMP and Executive Director at the MIT Center for Biomedical Innovation, added, “Our rapid method offers a more efficient way to not only detect microbial contamination but identify the contaminating species. We demonstrated that this method can deliver a high-sensitivity microbial sterility assessment within just 24 hours, providing a valuable tool for researchers and hopefully practitioners in the near future.”