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G462(P) Capturing t–cell receptors. a potential new modality for targeting hepatic tumours and post–transplantation lymphoproliferative disease (ptld)
  1. ND Ruth1,2,
  2. S Penny1,
  3. L Steadman1,
  4. D Millar1,
  5. D Hunt3,
  6. P Trantham3,
  7. D Kelly1,2,
  8. M Cobbold1
  1. 1School of Infection and Immunity, University of Birmingham Medical School, Birmingham, UK
  2. 2Hepatology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK
  3. 3Department of Chemistry, University of Virginia, USA

Abstract

Background The immune system plays an important part in recognising infection and diseases including cancer. Malignant cells express specific proteins on their cell surface. It is widely believed that it is these proteins that the immune system uses to recognise tumours and eventually eradicate them. When this process goes wrong, a tumour forms. The immune response to cancers in general is widely accepted to play an important role in control of tumorigenic processes, by using tumour infiltrating lymphocytes. How this process works is still being established, however there remains a potential target for cancer specific immunomodulatory treatment regimens.

Aim (1) To identify tumour specific MHC class I phosphopeptide antigens on lymphoblastoid cell lines LCL’s (an in vitro model for PTLD) as well as hepatic tumour tissues. (2) T-cells are immune cells which are notoriously difficult to maintain in long–term culture and as a result it is difficult to establish an ‘off the shelf’ T-cell product, however the aim of this project was to explore potential modalities for capturing the T-cell receptor (TCR), important in recognising tumour specific antigens and the resultant product could be used to establish a non patient–specific, but tumour specific product.

Patients and methods Paediatric and adult patients were identified with hepatic malignancy and consented as per current policy. Cells were isolated and tumour specific phosphopeptide antigens were identified. These provide the targets for T-cells, and more specifically TCR’s. Having identified these antigens, modalities have been explored for expanding these cells. Hybridoma technology is long established in immortalising B-cells, and this study aims to explore its potential with immortalisation of T-cells.

Results A number of novel phosphopeptide antigens have been identified both in vitro as well as on patient tissues. This information has been used to identify potential T-cell targets and by formation of hybridomas we have established a method for expanding specific T-cell’s in vitro. Although these hybridomas are currently unstable due to their tetraploid status, we aim to modify this protocol further to allow for stable expansion of hybridoma cells which possess the relevant TCR motif.

Conclusions Identifying a modality for expanding cells with a specific TCR repertoire clearly allows us to target tumour specific phosphopeptide antigens and has the potential to be developed as an immunomodulatory therapy in patients with hepatic tumours or PTLD.

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