title: Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy.
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.
authors.affiliation: Australian Centre for Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Corey
authors.initials: C
authors.lastname: Smith
authors.forename: Janice
authors.initials: J
authors.lastname: Tsang
authors.forename: Leone
authors.initials: L
authors.lastname: Beagley
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.forename: Victor
authors.initials: V
authors.lastname: Lee
authors.forename: Vivian
authors.initials: V
authors.lastname: Li
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Moss
authors.forename: William
authors.initials: W
authors.lastname: Coman
authors.forename: Kwok H
authors.initials: KH
authors.lastname: Chan
authors.forename: John
authors.initials: J
authors.lastname: Nicholls
authors.forename: Dora
authors.initials: D
authors.lastname: Kwong
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000328:Adult; D002277:Carcinoma; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000628:therapy*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D009362:Neoplasm Metastasis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1