Development of Adoptive immunotherapy of EBV-associated Malignancies by Retroviral LMP2-TCR Gene Transfer

Epstein Barr Virus (EBV) can cause several different types of cancer. There are currently no treatments available for some of these cancers. Our proposal is to take blood cells from patients with EBV-associated cancer and turn them into killer cells directed towards the cancer cells and then inject back into the patient. These killer cells will then be able to destroy the cancer cells and cure the patient.

Latent membrane protein-2 (LMP2) is an Epstein Barr Virus (EBV)-derived antigen that is expressed in approximately 40% of lymphomas, 10% gastric carcinomas and virtually all undifferentiated non-keratinising nasopharyngeal carcinomas (NPC) with poor prognosis. We propose to develop T cell receptor (TCR) gene therapy to generate LMP2-specific T cell populations for the treatment of EBV-associated lymphomas, gastric cancer and NPC. We have recently isolated the genes encoding the alpha and beta chain of a high avidity LMP2-specific TCR. The aim of the project will be to demonstrate that TCR-gene transfer efficiently generates LMP2-specific CD4+ and CD8+ T cell populations that are capable recognising tumour cells expressing LMP2 endogenously. Successful completion of the project will form the basis of a Phase I/II clinical trial in patients.