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

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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.