462. Serum Free Clinical Grade Large Scale Lentiviral Production System for Gene Therapy Application

Recently, lentiviral vectors have become the center of attention for its use as gene transfer vectors in gene therapy. Current new generation of therapies CAR - T requires the lentiviral vectors as efficient gene transfer tool to express engineered Chimeric Antigen Receptors (CAR) on the surface of the T-cells to recognize and kill the cancer cells. One problem of developing CAR T cell therapies is the high cost associated with lentiviral viral production. Therefore preclinical and clinical researchers have demanded their lentiviral production on a much larger scale, high-titer and in animal serum free medium. Current lentiviral production system use mainly adherent cells which need fetal bovine serum to support cell growth in flasks or cell factories, the system is suitable for research purpose at small scale, but not at large scale which requires large incubators and large cell culture vessels. Such system is hard to operator and requires more effort to produce large amount of LVVs, and increase the cost. We have developed a new lentiviral system to produce vectors in a serum free suspension platform and at very high titers. This technology employs a newly developed propriety set of GMP reagents comprising of a new media, new cells, new Transfection reagent and enhancers. With this new system we are able to deliver >5×10^8 (TU/ml) of unconcentrated lentiviral vectors, which is at least 10 folds higher than any other published method of lentiviral production. In this report, we will describe the methods and DOE experiments that we used to identify this new suite of reagent and their application in the immune cell therapy field.