We and others have demonstrated the feasibility of CTL therapy for EBV-positive NPC in immunocompetent patients, providing preliminary evidence of anti-tumor activity of EBV-CTL in this patient population. Not all patients responded, however, suggesting the need for further improvement. We propose that CTL failure can be overcome by increasing the specificity of the infused CTL product. That is, infusion of CTL specific for LMP1 and LMP2 will produce greater clinical benefit than EBV-specific CTL. The rationale for this approach is straight forward: EBV-specific CTL lines generated by standard methods are dominated by T-cell clones not reactive to the subdominant EBV proteins LMP1 and LMP2 expressed in NPC. We also propose that the failure of adoptively transferred CTL to measurably expand in the peripheral blood of NPC patients is a consequence both of lymphoid homeostasis in these lympho-replete patients and of the inhibitory T-cell infiltrate at the sites of disease. We will therefore use monoclonal antibodies targeting the CD45 antigen (CD45 MAbs), to lymphodeplete NPC patients prior to the infusion of EBV-specific CTL. Preliminary results indicate that CD45 MAb depletion can augment CTL expansion, and that such expansion is associated with a higher disease response rate. We will confirm and extend these promising new data in this Phase I clinical trial.