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

Chrystal U. Louis, Karin Straathof, Catherine M. Bollard, Sravya Ennamuri, Claudia Gerken, Teresita T. Lopez, M. Helen Huls, Andrea Sheehan, Meng Fen Wu, Hao Liu, Adrian Gee, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Stephen Gottschalk

Research output: Contribution to journalArticle

122 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)983-990
Number of pages8
JournalJournal of Immunotherapy
Volume33
Issue number9
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

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Adoptive Transfer
Human Herpesvirus 4
T-Lymphocytes
Antigens
Nasopharyngeal carcinoma
Disease Progression
Survival

Keywords

  • clinical trial
  • Epstein Barr Virus
  • nasopharyngeal carcinoma
  • T-cell immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

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.; Ennamuri, Sravya; Gerken, Claudia; Lopez, Teresita T.; Huls, M. Helen; Sheehan, Andrea; Wu, Meng Fen; Liu, Hao; Gee, Adrian; Brenner, Malcolm K.; Rooney, Cliona M.; Heslop, Helen E.; Gottschalk, Stephen.

In: Journal of Immunotherapy, Vol. 33, No. 9, 01.11.2010, p. 983-990.

Research output: Contribution to journalArticle

Louis, CU, Straathof, K, Bollard, CM, Ennamuri, S, Gerken, C, Lopez, TT, Huls, MH, Sheehan, A, Wu, MF, Liu, H, Gee, A, Brenner, MK, Rooney, CM, Heslop, HE & Gottschalk, S 2010, 'Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma', Journal of Immunotherapy, vol. 33, no. 9, pp. 983-990. https://doi.org/10.1097/CJI.0b013e3181f3cbf4
Louis, Chrystal U. ; Straathof, Karin ; Bollard, Catherine M. ; Ennamuri, Sravya ; Gerken, Claudia ; Lopez, Teresita T. ; Huls, M. Helen ; Sheehan, Andrea ; Wu, Meng Fen ; Liu, Hao ; Gee, Adrian ; Brenner, Malcolm K. ; Rooney, Cliona M. ; Heslop, Helen E. ; Gottschalk, Stephen. / Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. In: Journal of Immunotherapy. 2010 ; Vol. 33, No. 9. pp. 983-990.
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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.",
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AU - Liu, Hao

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