Use of lentivirus in individualized cell-gene therapy

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

This is a new project as of January 2021. The initial experiments are centered around establishing a baseline for comparison to the proposed lentiviral system and the development of the system and protocols to generate lentivirus suitable for clinical T-cell transductions. Critical variables of the lentivirus evaluation is the selection of promoter (EF1a, CMV or MSCV LTR), lentivirus production method (concentrated vs unconcentrated), transduction protocol (incubation vs spinoculation) and use (or concentration) of OKT3 required for T-cell stimulation and activation. Lentivirus production parameters have been determined and at-scale cell experiments have been performed with the intention of transitioning to a GMP production platform. The newly developed cell production process has reduced the T cell production time to 14 days and requires only 3 manipulations during that time frame. The T cell repertoire at the end of the new, shorter process more closely mimics the starting T cell sub-population ratios, with a continued bias towards younger, naive T cells. Mouse experiments are underway with a gamma-retroviral comparator to demonstrate clinical relevance of using lentivirus for TCR transgene delivery.