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Article: Effective treatment of metastatic forms of epstein-barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy

TitleEffective treatment of metastatic forms of epstein-barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy
Authors
Issue Date2012
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2012, v. 72 n. 5, p. 1116-1125 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/148689
ISSN
2014 Impact Factor: 9.329
2013 SCImago Journal Rankings: 5.627
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorSmith, Cen_HK
dc.contributor.authorTsang, Jen_HK
dc.contributor.authorBeagley, Len_HK
dc.contributor.authorChua, Den_HK
dc.contributor.authorLee, Ven_HK
dc.contributor.authorLi, Ven_HK
dc.contributor.authorMoss, DJen_HK
dc.contributor.authorComan, Wen_HK
dc.contributor.authorChan, KHen_HK
dc.contributor.authorNicholls, Jen_HK
dc.contributor.authorKwong, Den_HK
dc.contributor.authorKhanna, Ren_HK
dc.date.accessioned2012-05-29T06:14:42Z-
dc.date.available2012-05-29T06:14:42Z-
dc.date.issued2012en_HK
dc.identifier.citationCancer Research, 2012, v. 72 n. 5, p. 1116-1125en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148689-
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.en_HK
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshViral Matrix Proteins - immunologyen_HK
dc.subject.meshT-Lymphocytes, Cytotoxic - immunologyen_HK
dc.subject.meshNeoplasm Metastasisen_HK
dc.subject.meshNasopharyngeal Neoplasms - immunology - pathology - therapy - virologyen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshImmunization, Passiveen_HK
dc.subject.meshHumansen_HK
dc.subject.meshHerpesvirus 4, Human - immunologyen_HK
dc.subject.meshEpstein-Barr Virus Nuclear Antigens - immunologyen_HK
dc.subject.meshEpstein-Barr Virus Infections - immunology - therapyen_HK
dc.subject.meshDisease Progressionen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAdenoviridae - immunologyen_HK
dc.titleEffective treatment of metastatic forms of epstein-barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapyen_HK
dc.typeArticleen_HK
dc.identifier.emailTsang, J: jwhtsang@hku.hken_HK
dc.identifier.emailLee, V: vhflee@hku.hken_HK
dc.identifier.emailLi, V: livivian@hku.hken_HK
dc.identifier.emailNicholls, J: jmnichol@hkucc.hku.hk-
dc.identifier.emailKwong, D: dlwkwong@hku.hk-
dc.identifier.authorityTsang, J=rp00278en_HK
dc.identifier.authorityChua, D=rp00415en_HK
dc.identifier.authorityNicholls, J=rp00364en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1158/0008-5472.CAN-11-3399en_HK
dc.identifier.pmid22282657-
dc.identifier.scopuseid_2-s2.0-84863269918en_HK
dc.identifier.hkuros210217-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84863269918&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume72en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1116en_HK
dc.identifier.epage1125en_HK
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000300989100011-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKhanna, R=7202996651en_HK
dc.identifier.scopusauthoridKwong, D=54890371000en_HK
dc.identifier.scopusauthoridNicholls, J=7201463077en_HK
dc.identifier.scopusauthoridChan, KH=55230963800en_HK
dc.identifier.scopusauthoridComan, W=6701842615en_HK
dc.identifier.scopusauthoridMoss, DJ=7201847881en_HK
dc.identifier.scopusauthoridLi, V=8980838100en_HK
dc.identifier.scopusauthoridLee, V=54890729100en_HK
dc.identifier.scopusauthoridChua, D=7006773480en_HK
dc.identifier.scopusauthoridBeagley, L=6507699776en_HK
dc.identifier.scopusauthoridTsang, J=35141929400en_HK
dc.identifier.scopusauthoridSmith, C=7501653229en_HK

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