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Article: Effective treatment of metastatic forms of epstein-barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy
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TitleEffective treatment of metastatic forms of epstein-barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy
 
AuthorsSmith, C3
Tsang, J2
Beagley, L3
Chua, D4
Lee, V2
Li, V2
Moss, DJ3
Coman, W1
Chan, KH2
Nicholls, J2
Kwong, D2
Khanna, R3
 
Issue Date2012
 
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
CitationCancer Research, 2012, v. 72 n. 5, p. 1116-1125 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-11-3399
 
AbstractNasopharyngeal carcinoma (NPC) is endemic in China and Southeast Asia where it is tightly associated with infections by Epstein-Barr virus (EBV). The role of tumor-associated viral antigens in NPC renders it an appealing candidate for cellular immunotherapy. In earlier preclinical studies, a novel adenoviral vector-based vaccine termed AdE1-LMPpoly has been generated that encodes EBV nuclear antigen-1 (EBNA1) fused to multiple CD8(+) T-cell epitopes from the EBV latent membrane proteins, LMP1 and LMP2. Here, we report the findings of a formal clinical assessment of AdE1-LMPpoly as an immunotherapeutic tool for EBV-associated recurrent and metastatic NPC. From a total of 24 patients with NPC, EBV-specific T cells were successfully expanded from 16 patients with NPC (72.7%), whereas six patients with NPC (27.3%) showed minimal or no expansion of virus-specific T cells. Transient increase in the frequencies of LMP1and2- and EBNA1-specific T-cell responses was observed after adoptive transfer to be associated with grade I flu-like symptoms and malaise. The time to progression in these patients ranged from 38 to 420 days with a mean time to progression of 136 days. Compared with patients who did not receive T cells, the median overall survival increased from 220 to 523 days. Taken together, our findings show that adoptive immunotherapy with AdE1-LMPpoly vaccine is safe and well tolerated and may offer clinical benefit to patients with NPC.
 
ISSN0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
DOIhttp://dx.doi.org/10.1158/0008-5472.CAN-11-3399
 
ISI Accession Number IDWOS:000300989100011
Funding AgencyGrant Number
Ester Lee and Chew Pik Foundation
Croucher Foundation
National Health and Medical Research Council (Australia)
Funding Information:

This study was supported by funding from Ester Lee and Chew Pik Foundation, Croucher Foundation, and many other generous donors. R. Khanna is supported by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorSmith, C
 
dc.contributor.authorTsang, J
 
dc.contributor.authorBeagley, L
 
dc.contributor.authorChua, D
 
dc.contributor.authorLee, V
 
dc.contributor.authorLi, V
 
dc.contributor.authorMoss, DJ
 
dc.contributor.authorComan, W
 
dc.contributor.authorChan, KH
 
dc.contributor.authorNicholls, J
 
dc.contributor.authorKwong, D
 
dc.contributor.authorKhanna, R
 
dc.date.accessioned2012-05-29T06:14:42Z
 
dc.date.available2012-05-29T06:14:42Z
 
dc.date.issued2012
 
dc.description.abstractNasopharyngeal carcinoma (NPC) is endemic in China and Southeast Asia where it is tightly associated with infections by Epstein-Barr virus (EBV). The role of tumor-associated viral antigens in NPC renders it an appealing candidate for cellular immunotherapy. In earlier preclinical studies, a novel adenoviral vector-based vaccine termed AdE1-LMPpoly has been generated that encodes EBV nuclear antigen-1 (EBNA1) fused to multiple CD8(+) T-cell epitopes from the EBV latent membrane proteins, LMP1 and LMP2. Here, we report the findings of a formal clinical assessment of AdE1-LMPpoly as an immunotherapeutic tool for EBV-associated recurrent and metastatic NPC. From a total of 24 patients with NPC, EBV-specific T cells were successfully expanded from 16 patients with NPC (72.7%), whereas six patients with NPC (27.3%) showed minimal or no expansion of virus-specific T cells. Transient increase in the frequencies of LMP1and2- and EBNA1-specific T-cell responses was observed after adoptive transfer to be associated with grade I flu-like symptoms and malaise. The time to progression in these patients ranged from 38 to 420 days with a mean time to progression of 136 days. Compared with patients who did not receive T cells, the median overall survival increased from 220 to 523 days. Taken together, our findings show that adoptive immunotherapy with AdE1-LMPpoly vaccine is safe and well tolerated and may offer clinical benefit to patients with NPC.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationCancer Research, 2012, v. 72 n. 5, p. 1116-1125 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-11-3399
 
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-11-3399
 
dc.identifier.eissn1538-7445
 
dc.identifier.epage1125
 
dc.identifier.hkuros210217
 
dc.identifier.isiWOS:000300989100011
Funding AgencyGrant Number
Ester Lee and Chew Pik Foundation
Croucher Foundation
National Health and Medical Research Council (Australia)
Funding Information:

This study was supported by funding from Ester Lee and Chew Pik Foundation, Croucher Foundation, and many other generous donors. R. Khanna is supported by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship.

 
dc.identifier.issn0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
dc.identifier.issue5
 
dc.identifier.pmid22282657
 
dc.identifier.scopuseid_2-s2.0-84863269918
 
dc.identifier.spage1116
 
dc.identifier.urihttp://hdl.handle.net/10722/148689
 
dc.identifier.volume72
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofCancer Research
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshViral Matrix Proteins - immunology
 
dc.subject.meshT-Lymphocytes, Cytotoxic - immunology
 
dc.subject.meshNeoplasm Metastasis
 
dc.subject.meshNasopharyngeal Neoplasms - immunology - pathology - therapy - virology
 
dc.subject.meshMiddle Aged
 
dc.subject.meshImmunization, Passive
 
dc.subject.meshHumans
 
dc.subject.meshHerpesvirus 4, Human - immunology
 
dc.subject.meshEpstein-Barr Virus Nuclear Antigens - immunology
 
dc.subject.meshEpstein-Barr Virus Infections - immunology - therapy
 
dc.subject.meshDisease Progression
 
dc.subject.meshAdult
 
dc.subject.meshAdenoviridae - immunology
 
dc.titleEffective treatment of metastatic forms of epstein-barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy
 
dc.typeArticle
 
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<contributor.author>Lee, V</contributor.author>
<contributor.author>Li, V</contributor.author>
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<contributor.author>Chan, KH</contributor.author>
<contributor.author>Nicholls, J</contributor.author>
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Author Affiliations
  1. University of Queensland
  2. The University of Hong Kong
  3. Queensland Institute of Medical Research
  4. Hong Kong Sanatorium and Hospital