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