Adoptive Transfer of EBV-specific T Cells Results in Sustained Clinical Responses in Patients With Locoregional Nasopharyngeal Carcinoma.
Louis, Chrystal U. * + ++; Straathof, Karin *; Bollard, Catherine M. * + ++ [S] [//]; Ennamuri, Sravya * +; Gerken, Claudia * + ++; Lopez, Teresita T. *; Huls, M. Helen *; Sheehan, Andrea [//]; Wu, Meng-Fen [P]; Liu, Hao [P]; Gee, Adrian * + ++ [S]; Brenner, Malcolm K. * + ++ [S]; Rooney, Cliona M. * + ++ [//] [P]**; Heslop, Helen E. * + ++ [S]; Gottschalk, Stephen * + ++ [//]
Journal of Immunotherapy.
33(9):983-990, November/December 2010.
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Patients with recurrent or refractory Epstein Barr Virus (EBV)-positive nasopharyngeal carcinoma (NPC) continue to have poor outcomes. Our earlier Phase I dose escalation clinical study of 10 NPC patients showed that infusion of EBV-specific cytotoxic T cells (EBV-CTLs) was safe and had antitumor activity. To better define the overall response rate and discover whether disease status, EBV-antigen specificity, and/or in vivo expansion of infused EBV-CTLs predicted outcome, we treated 13 additional NPC patients with EBV-CTLs in a fixed-dose, Phase II component of the study. We assessed toxicity, efficacy, specificity, and expansion of infused CTLs for all 23 recurrent/refractory NPC patients treated on this Phase I/II clinical study. At the time of CTL infusion, 8 relapsed NPC patients were in remission and 15 had active disease. No significant toxicity was observed. Of the relapsed patients treated in their second or subsequent remission, 62% (5/8) remain disease free (at 17 to 75 mo), whereas 48.7% (7/15) of those with active disease had a CR/CRu (33.3%) or PR (15.4%). In contrast to locoregional disease, metastatic disease was associated with an increased risk of disease progression (HR: 3.91, P=0.015) and decreased overall survival (HR: 5.55, P=0.022). Neither the specificity of the infused CTLs for particular EBV antigens nor their measurable in vivo expansion discernibly influenced outcome. In conclusion, treatment of patients with relapsed/refractory EBV-positive NPC with EBV-CTLs is safe and can be associated with significant, long-term clinical benefit, particularly for patients with locoregional disease.
(C) 2010 Lippincott Williams & Wilkins, Inc.