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<https://discovery-pp.ucl.ac.uk/id/eprint/10167436> <http://purl.org/dc/terms/title> "The Bioprocessing of T cells and T cell Derived Extracellular Vesicles"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery-pp.ucl.ac.uk/id/eprint/10167436> <http://purl.org/ontology/bibo/abstract> "Cell and gene therapies have been gaining increasing interest over the years as a result of\r\npositive clinical outcomes. Most recently, genetically engineered T cells expressing CD19-\r\nchrimeric antigen receptor (CD19 CAR-T cells) have been hailed as ‘the cure for cancer’\r\nfollowing the 10-year remission of patients. However, the use of ‘living drugs’ for adoptive\r\ncell-based therapies warrants the risk of difficult to treat side-effects. Alternatively, γδT cells\r\nare extensively being studied in parallel for their unique innate/adaptive qualities in mitigating\r\nagainst the risk of off-target toxicities. Nevertheless, several researchers have sought to explore\r\nthe potential of immune cell-derived extracellular vesicles (EVs) as replacement upon the\r\ndiscovery of their ability to function as parent-cell mimics in absence of their producer cell.\r\nBoth γδT cell and CAR-T cell derived EVs have previously demonstrated in vivo cytotoxicity\r\nagainst target cells and at reduced toxicities when compared to their respective parent cell.\r\nAlthough, challenges associated with the bioprocessing of T cells and T cell products has\r\ncontributed to the delay of their clinical use.\r\nThis doctoral thesis sets out to explore and highlight the bioprocessing considerations required\r\nin producing T cells and T cell derived EVs for potential adoption within cancer\r\nimmunotherapy. This was attempted by assessing the ability to culture donor derived PBMC\r\nin serum-free conditions for the expansion of T cells. Furthermore, PBMC derived EVs were\r\nalso characterised and assessed for their cytotoxic potential against Nalm-6 (pre-B cell\r\nleukaemia) cell line. EVs harvested from day 6 of expanding PBMC in serum-free media\r\nshowed significant cytotoxic capabilities over EVs harvested at later timepoints. This was\r\nfound to be in agreement with the data obtained from CD19 CAR-T cell derived EVs whereby\r\nday 3 harvest contained significantly higher populations of cytotoxic proteins when compared\r\nto EVs harvested at day 7 of culture. However, in order to influence the production of cytotoxic\r\nEVs, γδT cells were exploited for their innate-like capabilities by developing LPS-coated beads\r\nfor their activation and production cytotoxic EVs. This was proven to be successful when\r\ncompared with / without the use of CD3/CD28-coated beads. This thesis provides novel insight\r\ninto methods of bioprocessing T cells and T cell derived EVs towards advancing the field of\r\ncancer immunotherapy."^^<http://www.w3.org/2001/XMLSchema#string> .
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