Treatment of nasopharyngeal carcinoma with Epstein-Barr virus–specific T lymphocytes

• Published in: Blood Vol. 105; no. 5; pp. 1898 - 1904
• Main Authors: Straathof, Karin C.M., Bollard, Catherine M., Popat, Uday, Huls, M.Helen, Lopez, Teresita, Morriss, M.Craig, Gresik, Mary V., Gee, Adrian P., Russell, Heidi V., Brenner, Malcolm K., Rooney, Cliona M., Heslop, Helen E.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.03.2005; The Americain Society of Hematology
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens, Viral; Applied cell therapy and gene therapy; Biological and medical sciences; Cell Culture Techniques; Herpesvirus 4, Human - immunology; Humans; Immunity; Immunotherapy, Adoptive - methods; Medical sciences; Nasopharyngeal Neoplasms - pathology; Nasopharyngeal Neoplasms - therapy; Nasopharyngeal Neoplasms - virology; Otorhinolaryngology. Stomatology; Remission Induction; T-Cell Antigen Receptor Specificity; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - transplantation; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Treatment Outcome; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Viral Load; Gammaherpesvirinae; Antineoplastic agent; Human; Cell therapy; Herpesviridae; Epstein Barr virus; Malignant tumor; Nasopharynx carcinoma; Infection; Virus; Treatment; Immunotherapy; Viral disease; ENT disease; Pharynx disease; Cytotoxic T lymphocyte
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-07-2975

Conventional treatment for nasopharyngeal carcinoma (NPC) frequently fails and is accompanied by severe long-term side effects. Since virtually all undifferentiated NPCs are associated with Epstein-Barr virus (EBV), this tumor is an attractive candidate for cellular immunotherapy targeted against tumor-associated viral antigens. We now demonstrate that EBV-specific cytotoxic T-cell (CTL) lines can readily be generated from individuals with NPC, notwithstanding the patients' prior exposure to chemotherapy/radiation. A total of 10 patients diagnosed with advanced NPC were treated with autologous CTLs. All patients tolerated the CTLs, although one developed increased swelling at the site of pre-existing disease. At 19 to 27 months after infusion, 4 patients treated in remission from locally advanced disease remain disease free. Of 6 patients with refractory disease prior to treatment, 2 had complete responses, and remain in remission over 11 to 23 months after treatment; 1 had a partial remission that persisted for 12 months; 1 has had stable disease for more than 14 months; and 2 had no response. These results demonstrate that administration of EBV-specific CTLs to patients with advanced NPC is feasible, appears to be safe, and can be associated with significant antitumor activity.