Retroviral transduction of a T cell receptor specific for an Epstein-Barr virus-encoded peptide

The Type II EBV malignancies nasopharyngeal carcinoma and EBV+ Hodgkin's di sease express three subdominant antigens, latency membrane protein (LMP) 1, LMP2, and EBNA-1, While adoptive immunotherapy with T cell lines for Type III EBV malignancy (such as posttransplant lymphoma, PTLD, which expresses the immunodominant EBNA-3 antigens) has been used to prevent and treat PTLD , the generation of class I MHC-restricted CTL suitable for the immunothera py of Type II EBV malignancy is difficult. This is primarily due to the lac k of anti-LMP or EBNA-1 CTL activity in many healthy volunteers. We have en gineered, by retroviral transduction of the TCR, CTL that have the potentia l to recognize subdominant EBV latency antigens, Using the SAMEN retroviral vector we demonstrate the ability to transfer CTL activity from a LMP2 pep tide-specific CTL clone to a stimulated PBMC population. TCR-transduced PBM C also secrete IFN-gamma upon coculture with LMP2 targets and maintain expr ession of the transduced TCR during subsequent mitogenic expansion. (C) 200 1 Academic Press.