Document Detail


Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma.
MedLine Citation:
PMID:  20948438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  Clinical Trial, Phase I; Clinical Trial, Phase II; Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunotherapy (Hagerstown, Md. : 1997)     Volume:  33     ISSN:  1537-4513     ISO Abbreviation:  J. Immunother.     Publication Date:    2010 Nov-Dec
Date Detail:
Created Date:  2010-10-26     Completed Date:  2011-05-24     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  9706083     Medline TA:  J Immunother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  983-90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Antigens, Viral / immunology
Carcinoma / diagnosis*,  immunology*,  pathology,  physiopathology,  therapy
Cell Proliferation
Child
Disease Progression
Disease-Free Survival
Female
Herpesvirus 4, Human / immunology*,  pathogenicity
Humans
Immunotherapy, Adoptive*
Male
Middle Aged
Nasopharyngeal Neoplasms / diagnosis*,  immunology*,  pathology,  physiopathology,  therapy
Neoplasm Metastasis
Neoplasm Recurrence, Local
Prognosis
T-Lymphocytes, Cytotoxic / immunology,  metabolism*,  pathology
Treatment Outcome
Grant Support
ID/Acronym/Agency:
K12 CA090433/CA/NCI NIH HHS; K12 CA09043306/CA/NCI NIH HHS; P01 CA94237/CA/NCI NIH HHS; RR00188/RR/NCRR NIH HHS; T32 DK064717/DK/NIDDK NIH HHS; T32 DK64717/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Viral
Comments/Corrections

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