Capturing T-cell receptors - a potential new modality for targeting hepatic tumours and post-transplantational lymphoproliferative disease (PLTD)

Ruth, Nicola Dawn (2018). Capturing T-cell receptors - a potential new modality for targeting hepatic tumours and post-transplantational lymphoproliferative disease (PLTD). University of Birmingham. Ph.D.

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Abstract

This project sought to identify paediatric tumour-specific phosphopeptide antigens on Post-transplantation lymphoproliferative disease samples (PTLD) and hepatic tumour samples. Tumour-specific T-cells are difficult to maintain in long-term culture, therefore the secondary aim of this project was exploring modalities for capturing T-cell receptor (TCR), important in recognising tumour-specific antigens. This may result in a tumour-specific product. Potential modalities included T-cell hybridomas and Human Induced Pluripotent Stem Cell (hIPSc) technology to immortalise tumour specific T-cells.
As a result, we have developed a technology for expanding these and differentiating them into a T-cell of interest with potential for future clinical application in paediatric tumours, using OP9 DL1 mouse feeder cell system to support differentiation of hIPSc towards haemopoietic lineage, demonstrating functionality of the end stage ‘T-cell product’.
In summary we have identified a number of novel phosphopeptide antigens in vitro as well as on patient tissues. This information has been used to identify potential T-cell targets and by formation of hIPSc we have established a method for expanding specific T-cell’s in vitro. Using OP9DL1 cells we have also identified a method for differentiating these cells into lymphocyte-like cells with T-cell functionality therefore representing a possible methodology for expanding tumour-specific T-cells for clinical application.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):