Zheng, Y., Machado, L., Johnson, B., James, C., Parsonage, G. and Lee, S. P. (2010) EBV-specific T cell receptor gene transfer to target nasopharyngeal carcinoma. Poster presented to: 14th Biennial Conference of the International Association for Research on Epstein-Barr Virus and Associated Diseases, University of Birmingham, 04-07 September 2010. (Unpublished)
| Item Type: | Conference or Workshop Item (Poster) |
|---|---|
| Abstract: | Infusing EBV-specific T cells is an effective prophylactic and therapeutic treatment for EBV post transplant lymphoproliferative disease. However, extending this approach to treat NPC necessitates targeting viral antigens that are subdominant targets for T cells. Therefore we have explored the use of T cell receptor (TCR) gene transfer to rapidly and reliably generate such T cell responses from all patients. To ensure a widely applicable treatment we cloned the genes encoding the TCR from an LMP2- specific T cell that is restricted through HLA A*1101, an allele carried by >50% of the Chinese population. Genes encoding the TCR α and β chains were cloned into a single retroviral vector, separated by a self-cleaving 2A peptide to ensure equal expression. T cells were transduced with this retrovirus and within 3-5 days HLA:peptide pentamer staining detected the transferred TCR in 12-17% of CD8+ T cells and 7-12% of CD4+ T cells. TCR-transduced T cells expanded rapidly in vitro in response to antigen and showed high avidity for the target peptide (10-10M) in assays of interferon-γ release. To improve safety and efficacy, the TCR was modified by codon optimization and introduction of an additional disulphide-bond. This increased almost two-fold the proportion of T cells expressing the receptor. TCR-transduced CD4+ T cells produced multiple cytokines (including IL2) in response to LMP2 suggesting they could provide a helper function in vivo to aid persistence of CD8+ effectors. Both CD8+ and CD4+ transduced T cells lysed an A11+ NPC cell line expressing LMP2. |
| Subjects: |
Q Science > QR Microbiology > QR355 Virology R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology R Medicine > RM Therapeutics. Pharmacology > RM270 Immunotherapy. Serotherapy |
| Creators: | Zheng, Y, Machado, Lee, Johnson, B, James, C, Parsonage, Greg and Lee, S P |
| Northamptonshire and East Midlands: | Health |
| Faculties, Divisions and Institutes: |
University Faculties, Divisions and Research Centres - OLD > Faculty of Health & Society > Sports, Exercise & Life Sciences University Faculties, Divisions and Research Centres - OLD > Research Centre > Institute of Health and Wellbeing > Ageing Research Centre Faculties > Faculty of Health & Society > Sports, Exercise & Life Sciences Research Centres > Centre for Health Sciences and Services Research Centres > Centre for Physical Activity and Life Sciences |
| Date: | 2010 |
| Date Type: | Presentation |
| Event Title: | 14th Biennial Conference of the International Association for Research on Epstein-Barr Virus and Associated Diseases |
| Event Dates: | 04-07 September 2010 |
| Event Location: | University of Birmingham |
| Event Type: | Conference |
| Language: | English |
| Status: | Unpublished |
| URI: | http://nectar.northampton.ac.uk/id/eprint/6853 |
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