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Title: Preclinical development of adoptive T-cell immunotherapy for EBV-associated diseases using third-party donors
Author: Frumento, Guido
ISNI:       0000 0004 7426 2062
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2018
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A significant number of patients requiring adoptive T-cell therapy (ATCT) need to resort to third party donors; we aimed to find ways to optimise ATCT from third party donors in EBV-associated diseases. Firstly, we evaluated the T-cell response to 29 EBV-restricted peptides in a cohort of 100 healthy donors. For each peptide we found at least one high-responding donor. Also, we compared the efficacy of different separation techniques. These results support the setting up of a registry of third party donors, to provide fresh EBV-specific T cells for ATCT. Secondly, we investigated the mechanisms generating T memory stem cells (TSCM), which are considered most suitable for ATCT. We demonstrated that homeostatic cytokines revert recently differentiated CD8⁺ memory T cells from cord blood (CB) to cells with a TN-like phenotype (TNrev) and TSCM-like characteristics. Finally, we compared phenotype and function of CD8⁺ T cells from peripheral blood and CB, after transduction of an EBV-specific TCR. Transduction efficiency, growth kinetics and cytolytic activity were comparable. However, TCR-transduced CB T cells showed less differentiated phenotype, increased multi-cytokine expression, and lacked expression of the senescence marker CD57. These data suggest that survival of engineered T cells in vivo is likely to be improved by using cells from CB.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RA0421 Public health. Hygiene. Preventive Medicine ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)