Title |
Effective Treatment of Metastatic Forms of Epstein-Barr Virus–Associated Nasopharyngeal Carcinoma with a Novel Adenovirus-Based Adoptive Immunotherapy
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Published in |
Cancer Research, March 2012
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DOI | 10.1158/0008-5472.can-11-3399 |
Pubmed ID | |
Authors |
Corey Smith, Janice Tsang, Leone Beagley, Daniel Chua, Victor Lee, Vivian Li, Denis J. Moss, William Coman, Kwok H. Chan, John Nicholls, Dora Kwong, Rajiv Khanna |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Hong Kong | 1 | 1% |
Unknown | 89 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 19 | 21% |
Researcher | 10 | 11% |
Student > Master | 10 | 11% |
Student > Bachelor | 9 | 10% |
Other | 4 | 4% |
Other | 17 | 19% |
Unknown | 21 | 23% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 25 | 28% |
Agricultural and Biological Sciences | 14 | 16% |
Immunology and Microbiology | 8 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 6% |
Biochemistry, Genetics and Molecular Biology | 5 | 6% |
Other | 8 | 9% |
Unknown | 25 | 28% |