Use of lentivirus in individualized cell-gene therapy

Division Of Basic Sciences - Nci

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Abstract

AIM 1 This successful completion of this aim has been reported in the previous year's annual reports. AIM 2 During this reporting period, a cell production pipeline utilizing lentivirus that reduced manufacturing time and preserved/augmented a greater percentage of undifferentiated T cells (phenotype) was developed. Variables that were tested and changed/incorporated include enrichment strategies prior to activation, T cell activation reagents, addition of cytokines, transduction conditions, and expansion strategies. Collectively, using design of experiment a final two-week protocol has been established which can consistently produce a final product composition conserving T cell subtype ratios, undifferentiated phenotypes and lower effector memory population percentages. Reported transduction efficiencies in the final product (using a reasonable MOI) were appropriate for clinical use. The future work planned to culminate this project will evaluate selection of transduced cells and maintenance of desired phenotype to deliver a near 100% transduced cell product potentially further improving on timeline and cell number.