Article: Effective treatment of metastatic forms of epstein-barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy
| Title | Effective treatment of metastatic forms of epstein-barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Authors | Smith, C3 Tsang, J2 Beagley, L3 Chua, D4 Lee, V2 Li, V2 Moss, DJ3 Coman, W1 Chan, KH2 Nicholls, J2 Kwong, D2 Khanna, R3 | ||||||||
| Issue Date | 2012 | ||||||||
| Publisher | American 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?] DOI: http://dx.doi.org/10.1158/0008-5472.CAN-11-3399 | ||||||||
| Abstract | Nasopharyngeal 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. | ||||||||
| ISSN | 0008-5472 2011 Impact Factor: 7.856 2011 SCImago Journal Rankings: 1.309 | ||||||||
| DOI | http://dx.doi.org/10.1158/0008-5472.CAN-11-3399 | ||||||||
| ISI Accession Number ID | WOS:000300989100011
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 | References in Scopus |
| dc.contributor.author | Smith, C | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Tsang, J | ||||||||
| dc.contributor.author | Beagley, L | ||||||||
| dc.contributor.author | Chua, D | ||||||||
| dc.contributor.author | Lee, V | ||||||||
| dc.contributor.author | Li, V | ||||||||
| dc.contributor.author | Moss, DJ | ||||||||
| dc.contributor.author | Coman, W | ||||||||
| dc.contributor.author | Chan, KH | ||||||||
| dc.contributor.author | Nicholls, J | ||||||||
| dc.contributor.author | Kwong, D | ||||||||
| dc.contributor.author | Khanna, R | ||||||||
| dc.date.accessioned | 2012-05-29T06:14:42Z | ||||||||
| dc.date.available | 2012-05-29T06:14:42Z | ||||||||
| dc.date.issued | 2012 | ||||||||
| dc.description.abstract | Nasopharyngeal 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.nature | Link_to_subscribed_fulltext | ||||||||
| dc.identifier.citation | Cancer 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.doi | http://dx.doi.org/10.1158/0008-5472.CAN-11-3399 | ||||||||
| dc.identifier.epage | 1125 | ||||||||
| dc.identifier.hkuros | 210217 | ||||||||
| dc.identifier.isi | WOS:000300989100011
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.issn | 0008-5472 2011 Impact Factor: 7.856 2011 SCImago Journal Rankings: 1.309 | ||||||||
| dc.identifier.issue | 5 | ||||||||
| dc.identifier.pmid | 22282657 | ||||||||
| dc.identifier.scopus | eid_2-s2.0-84863269918 | ||||||||
| dc.identifier.spage | 1116 | ||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/148689 | ||||||||
| dc.identifier.volume | 72 | ||||||||
| dc.language | eng | ||||||||
| dc.publisher | American Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/ | ||||||||
| dc.publisher.place | United States | ||||||||
| dc.relation.ispartof | Cancer Research | ||||||||
| dc.relation.references | References in Scopus | ||||||||
| dc.subject.mesh | Viral Matrix Proteins - immunology | ||||||||
| dc.subject.mesh | T-Lymphocytes, Cytotoxic - immunology | ||||||||
| dc.subject.mesh | Neoplasm Metastasis | ||||||||
| dc.subject.mesh | Nasopharyngeal Neoplasms - immunology - pathology - therapy - virology | ||||||||
| dc.subject.mesh | Middle Aged | ||||||||
| dc.subject.mesh | Immunization, Passive | ||||||||
| dc.subject.mesh | Humans | ||||||||
| dc.subject.mesh | Herpesvirus 4, Human - immunology | ||||||||
| dc.subject.mesh | Epstein-Barr Virus Nuclear Antigens - immunology | ||||||||
| dc.subject.mesh | Epstein-Barr Virus Infections - immunology - therapy | ||||||||
| dc.subject.mesh | Disease Progression | ||||||||
| dc.subject.mesh | Adult | ||||||||
| dc.subject.mesh | Adenoviridae - immunology | ||||||||
| dc.title | Effective treatment of metastatic forms of epstein-barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy | ||||||||
| dc.type | Article |
Author Affiliations
- University of Queensland
- The University of Hong Kong
- Queensland Institute of Medical Research
- Hong Kong Sanatorium and Hospital