Development of a stable, continuous lentiviral (LV) production system for improved gene delivery and cell function

Scalable and consistent production of stable cell lines for improved lentiviral (LV) vector production is necessary to ensure sufficient supply of high-quality vector for gene therapies and gene-modified cell therapies. This requires an integrated approach with both biological engineering of the cell lines and bioprocess engineering of the upstream and downstream processing being considered in parallel.

From a biological engineering perspective, the project will seek to develop viral vectors which enable the simultaneous transduction and stimulation of T-cells (LentiStim) without the need for Dynabeads or antibodies in addition to undertaking a systematic, comparative study of various viral envelopes for enhanced T-cell engineering. From a bioprocessing perspective, the project will seek to establish a scalable bioprocess for the production of LentiStim viral vectors with the optimal viral envelope and develop an end-to-end process whereby the produced LV will be used to transduce primary T-cells with a chimeric antigen receptor (CAR). The T-cells produced from this process will be tested for anti-tumour efficacy in humanized mouse models. This will be established using NOD/SCID/IL2rynull (NSG) mouse model resistant to graft versus host disease with a B cell lymphoma cell line (Raji) or/and primary lymphoma cells.