Magnetic Ratcheting Cytometry Towards Manafacturing Scale Separations Of “Best In Class” Cart-T Cells
January 15-19, 2017
Adoptive cell therapies taking advantage of engineered Chimeric Antigen Receptors (CAR) or T-Cell Receptors (TCR) have shown incredible potential as “living drugs” that achieve personalized immunotherapies for cancer patients. However, variations in T cell transduction efficiency during genetic modification can lead to widely varied levels of expression (~2-orders of magnitude) which can possibly dilute therapeutic effectiveness and potentially contribute to off-tumor toxicity. While research has shown that isolation of cell sub-populations with tightly controlled expression could lead to improved therapies, limitations of current cell separation technologies prevent implementation at manufacturing scale workflows. Quantitative separation techniques (e.g. fluorescence assisted cell separation-FACS) do not scale for production of therapeutic doses, and magnetic assisted cell separation (MACS) techniques do not allow precise selection of cell sub-populations based on surface expression. Because of these limitations, enrichment of “best in class” CAR-T/TCR sub-populations at manufacturing scale throughputs remains impractical and non-economical.
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Coleman Murray, Edward Pao, Ximin Chen, Yvonne Chen, and Dino Di Carlo, "Magnetic Ratcheting Cytometry Towards Manafacturing Scale Separations Of “Best In Class” Cart-T Cells" in "Scale-up and Manufacturing of Cell-based Therapies V", Tom Brieva, Celgene Cellular Therapeutics William Miller, Northwestern University Chris Mason, University College London Eds, ECI Symposium Series, (2017). http://dc.engconfintl.org/cellbasedtherapies_v/110