Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel Adenovirus-based adoptive immunotherapy

Smith, Corey, Tsang, Janice, Beagley, Leone, Chua, Daniel, Lee, Victor, Li, Vivian, Moss, Denis J., Coman, William, Chan, Kwok H., Nicholls, John, Kwong, Dora and Khanna, Rajiv (2012) Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel Adenovirus-based adoptive immunotherapy. Cancer Research, 72 5: 1116-1125. doi:10.1158/0008-5472.CAN-11-3399


Author Smith, Corey
Tsang, Janice
Beagley, Leone
Chua, Daniel
Lee, Victor
Li, Vivian
Moss, Denis J.
Coman, William
Chan, Kwok H.
Nicholls, John
Kwong, Dora
Khanna, Rajiv
Title Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel Adenovirus-based adoptive immunotherapy
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
1538-7445
Publication date 2012-03-01
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-11-3399
Open Access Status Not yet assessed
Volume 72
Issue 5
Start page 1116
End page 1125
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Formatted 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 LMP1&2- 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.
Keyword Cytotoxic T-Cells
Ebv-Specific Ctl
Lymphoproliferative Disease
Transplant Recipients
Npc Patients
Responses
Lymphocytes
Polyepitope
Infection
Oncogene
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online first January 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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