Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma

J Immunother. Nov-Dec 2010;33(9):983-90. doi: 10.1097/CJI.0b013e3181f3cbf4.

Abstract

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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Viral / immunology
  • Carcinoma / diagnosis*
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Carcinoma / physiopathology
  • Carcinoma / therapy
  • Cell Proliferation
  • Child
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Herpesvirus 4, Human / immunology*
  • Herpesvirus 4, Human / pathogenicity
  • Humans
  • Immunotherapy, Adoptive*
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / diagnosis*
  • Nasopharyngeal Neoplasms / immunology*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / physiopathology
  • Nasopharyngeal Neoplasms / therapy
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Prognosis
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Cytotoxic / pathology
  • Treatment Outcome

Substances

  • Antigens, Viral