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Annals of Oncology 15:113-117, 2004
© 2004 European Society for Medical Oncology

Original Paper

Adoptive transfer of allogeneic Epstein–Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma

Received 23 July 2003; revised 4 September 2003; accepted 17 September 2003

Background:

The outcome of patients with nasopharyngeal carcinoma (NPC) presenting as advanced-stage disease or failing conventional radio-chemotherapy is poor. Thus, additional forms of effective, low-toxicity treatment are warranted to improve NPC prognosis. Since NPC is almost universally associated with Epstein–Barr virus (EBV), cellular immunotherapy with EBV-specific cytotoxic T lymphocytes (CTLs) may prove a successful treatment strategy.

Patient and methods

A patient with relapsed NPC, refractory to conventional treatments, received salvage adoptive immunotherapy with EBV-specific CTLs reactivated ex vivo from a human leukocyte antigen-identical sibling. EBV-specific immunity, as well as T-cell repertoire in the tumor, before and after immunotherapy, was evaluated.

Results:

CTL transfer was well tolerated, and a temporary stabilization of disease was obtained. Moreover, notwithstanding the short in-vivo duration of allogeneic CTLs, immunotherapy induced a marked increase of endogenous tumor-infiltrating CD8+ T lymphocytes, and a long-term increase of latent membrane protein 2-specific immunity.

Conclusions:

Preliminary data obtained in this patient indicate that EBV-specific CTLs are safe, may exert specific killing of NPC tumor cells in vitro, and induce antitumor effect in vivo.

P. Comoli1,*, R. De Palma2, S. Siena3, A. Nocera4, S. Basso1, F. Del Galdo2, R. Schiavo3, O. Carminati3, A. Tagliamacco4, G. F. Abbate2, F. Locatelli1, R. Maccario1 and P. Pedrazzoli3

1 Laboratory of Transplant Immunology and Pediatric Hematology/Oncology, IRCCS Policlinico S. Matteo, Pavia; 2 Department of Clinical and Experimental Medicine, Second University of Napoli; 3 Divisione di Oncologia Medica Falck, Department of Oncology, Ospedale Niguarda Ca’ Granda, Milano; 4 Transplant Immunology Unit, S. Martino Hospital, Genova, Italy

Key words: cellular immunotherapy, cytotoxic T lymphocytes, Epstein–Barr virus, latent membrane protein 2, nasopharyngeal carcinoma


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