Enabling High Yield Engineered T Cell Production by Quantitative Separation using Parallel Magnetic Ratcheting

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Project Summary: Enabling High Yield Engineered T Cell Production by Quantitative Separation using Parallel Magnetic Ratcheting Personalized cancer treatments are a growing area of research in the fight against cancer. One promising approach has been the use of engineered T cells to trigger the body’s immune system to directly attack the cancer. Recent research into chimeric antigen receptor (CAR) T cells has shown efficacy in treating B-cell malignancy and several other types of cancers. However, CAR-T cell production faces inherent challenges with transduction heterogeneity, leading to large variations in performance of engineered T cells. Research suggests that CAR-T cell therapies can be improved by separating only therapeutically optimal cells. Unfortunately, traditional methods of cell separation and analysis, including magnetic assisted cell separation (MACS) and fluorescence assisted cell separation (FACS), have inherent limitations in manufacture of CAR-T cell therapies. MACS techniques are Boolean in nature and cannot be used to enrich sub-populations based on expression of a surface marker. Alternatively, FACS techniques are highly quantitative, but cannot be practically scaled to meet an acceptable manufacturing throughput. Ferrologix aims to address the limitations in current CAR-T production methods by developing a commercial product based on a magnetic micromanipulation technique, known as magnetic ratcheting, developed at UCLA by the PI. This innovative technology imparts FACS’ quantitative analysis and separation capabilities to magnetic cell separation, enabling magnetically labeled cells to be separated based on the number of particles bound to their surface. Ferrologix aims to implement this quantitative magnetic separation technology into a cell separation instrument with disposable cartridges capable of quantitatively enriching therapeutically optimal CAR-T cells at industrial scale throughputs. If received, the phase I funds will be used to develop a prototype system to quantitatively separate CAR-T cells at a 105 cell/s throughput based on surface expression and will serve as validation for a cell manufacturing technology to improve the effectiveness of emerging cellular immunotherapies.