Autologous EBV-specific cytotoxix T lymphocytes for the treatment of EBV-related nasopharyngeal carcinoma

Abstract

2512 Background: nasopharyngeal carcinoma (NPC) is an EBV-related neoplasm expressing a limited number of viral antigens, including latent membrane protein 2 (LMP-2). Currently, the outcome of patients relapsing after first-line therapy is poor. Thus, alternative forms of effective, low-toxicity treatment are warranted. Based on successful experiences of immunotherapy for EBV-posttransplant lymphoproliferative disease, we explored the feasibility and safety of a T-cell therapy approach with EBV-specific CTLs as salvage therapy for NPC. Methods: our pilot clinical study has included 7 patients with advanced-stage EBV-related NPC with disease in progression after conventional therapies. CTL lines were reactivated and expanded from autologous peripheral blood lymphocytes, and were predominantly CD3+/CD8+ T-cells, displaying specific killing of autologous EBV-LCL, and, in 3 patients, showing a measurable lysis of LMP-2-bearing targets and patient tumor cells. Results: patients have been treated with 2–23 injections of EBV-specific CTL. T-cell transfer was well tolerated, and coincided with clinical benefit in 4 of 7 patients (2 partial responses, 2 disease stabilization). Analysis of IFN-γ producing cells demonstrated an increased frequency of EBV-specific immunity after immunotherapy, with sizeable LMP-2-specific responses in 3 patients. Conclusions: our data indicate that autologous EBV-specific CTLs can be used safely, are able to increase LMP-2-specific responses and exert in vivo anti-tumor immune surveillance in NPC patients. No significant financial relationships to disclose.