Magnetic Ratcheting Cytometry Towards Manafacturing Scale Separations Of “Best In Class” Cart-T Cells

Conference Dates

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[1] (~2-orders of magnitude) which can possibly dilute therapeutic effectiveness and potentially contribute to off-tumor toxicity[2]. While research has shown that isolation of cell sub-populations with tightly controlled expression could lead to improved therapies[3], 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.

[1] Chang ZL, Silver PA, Chen YY. Identification and selective expansion of functionally superior T cells expressing chimeric antigen receptors. J Transl Med. 2015;13:161. doi:10.1186/s12967-015-0519-8.

[2] Carels N, Spinassé LB, Tilli TM, Tuszynski JA. Toward precision medicine of breast cancer. Theor Biol Med Model. 2016;13:7. doi:10.1186/s12976-016-0035-4.

[3] Berger C, Jensen MC, Lansdorp PM, Gough M, Elliott C, Riddell SR. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Investig 2008;118: 294–305.

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