Originally published as JCO Early Release 10.1200/JCO.2005.02.6195 on October 3 2005

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Cell Therapy of Stage IV Nasopharyngeal Carcinoma With Autologous Epstein-Barr Virus–Targeted Cytotoxic T Lymphocytes

Patrizia Comoli, Paolo Pedrazzoli, Rita Maccario, Sabrina Basso, Ornella Carminati, Massimo Labirio, Roberta Schiavo, Simona Secondino, Chiara Frasson, Cesare Perotti, Mauro Moroni, Franco Locatelli, Salvatore Siena

From the Laboratorio di Ricerca Area Trapianti e Oncoematologia Pediatrica, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo; Servizio Trasfusionale, IRCCS Policlinico S. Matteo, Pavia; SC Divisione Oncologia Medica Falck, Ospedale Niguarda Ca' Granda, Milan, Italy

Address reprint requests to Patrizia Comoli, MD, Laboratorio di Ricerca Area Trapianti e Oncoematologia Pediatrica, IRCCS Policlinico S. Matteo, V.le Golgi 19, 27100 Pavia, Italy; e-mail: pcomoli{at}smatteo.pv.it with CC to salvatore.siena{at}ospedaleniguarda.it.

PURPOSE: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) –related malignancy expressing EBV antigens that are possible targets of cell therapy, including latent membrane protein 2 (LMP2). We conducted a clinical trial of EBV-targeted cell therapy with autologous virus-specific cytotoxic T lymphocytes (CTLs) for NPC refractory to conventional treatments.

PATIENTS AND METHODS: Ten patients with EBV-related stage IV NPC in progression after conventional radiotherapy and chemotherapy received intravenously autologous EBV-specific CTLs reactivated and expanded ex vivo from peripheral blood lymphocytes through stimulation with EBV-transformed autologous B-lymphoblastoid cell lines (LCL). Toxicity, specific cellular immune responses, and clinical tumor responses were evaluated.

RESULTS: EBV-specific CTLs could be generated in all patients and were predominantly CD3⁺/CD8⁺ T lymphocytes displaying specific killing of autologous EBV-LCL, autologous NPC cells as well as autologous targets bearing the EBV antigen LMP2. Patients received two to 23 infusions of EBV-specific CTLs that were well tolerated with the exception of grade 1 to 2 inflammatory reactions at the tumor site in two cases. Control of disease progression was obtained in six of 10 patients (two with partial response and four with stable disease). Analysis of interferon-–producing cells demonstrated an increased frequency of EBV-specific immunity, with appearance of LMP2-specific responses in four patients, of whom three had clinical benefit.

CONCLUSION: Cell therapy with EBV-targeted autologous CTLs is safe, induces LMP-2-specific immunologic responses, and is associated with objective responses and control of disease progression in patients with stage IV NPC resistant to conventional treatments.

Supported in part by grants from the Associazione Italiana Ricerca sul Cancro to P.C., F.L., R.M., and P.P.; Grants No. RFM/02, RFM/03, RFM/04 to P.C., F.L., R.M.; Grant No. FP6-Allostem to F.L.; and a grant from Oncologia Ca' Granda Organizzazione Non Lucrativa de Utilitá Social to P.P. and S.S. S.B. is the recipient of a grant from Associazione Morgan di Gianvittorio.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005.

P.C. and P.P. contributed equally to this work.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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