Document Detail

Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients.
MedLine Citation:
PMID:  23348421     Owner:  NLM     Status:  MEDLINE    
Epstein-Barr virus (EBV) is associated with several malignancies including nasopharyngeal carcinoma, a high incidence tumor in Chinese populations, in which tumor cells express the two EBV antigens EB nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). Here, we report the phase I trial of a recombinant vaccinia virus, MVA-EL, which encodes an EBNA1/LMP2 fusion protein designed to boost T-cell immunity to these antigens. The vaccine was delivered to Hong Kong patients with nasopharyngeal carcinoma to determine a safe and immunogenic dose. The patients, all in remission more than 12 weeks after primary therapy, received three intradermal MVA-EL vaccinations at three weekly intervals, using five escalating dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming unit (pfu). Blood samples were taken during prescreening, immediately before vaccination, one week afterward and at intervals up to one year later. Immunogenicity was tested by IFN-γ ELIspot assays using complete EBNA1 and LMP2 15-mer peptide mixes and known epitope peptides relevant to patient MHC type. Eighteen patients were treated, three per dose level one to four and six at the highest dose, without dose-limiting toxicity. T-cell responses to one or both vaccine antigens were increased in 15 of 18 patients and, in many cases, were mapped to known CD4 and CD8 epitopes in EBNA1 and/or LMP2. The range of these responses suggested a direct relationship with vaccine dose, with all six patients at the highest dose level giving strong EBNA1/LMP2 responses. We concluded that MVA-EL is both safe and immunogenic, allowing the highest dose to be forwarded to phase II studies examining clinical benefit.
Edwin P Hui; Graham S Taylor; Hui Jia; Brigette B Y Ma; Stephen L Chan; Rosalie Ho; Wai-Lap Wong; Steven Wilson; Benjamin F Johnson; Ceri Edwards; Deborah D Stocken; Alan B Rickinson; Neil M Steven; Anthony T C Chan
Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-24
Journal Detail:
Title:  Cancer research     Volume:  73     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-18     Completed Date:  2013-08-05     Revised Date:  2014-07-22    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1676-88     Citation Subset:  IM    
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MeSH Terms
Antigens, Viral / immunology*
Cancer Vaccines / therapeutic use*
Enzyme-Linked Immunosorbent Assay
Herpesvirus 4, Human / immunology*
Middle Aged
Nasopharyngeal Neoplasms / therapy*
Vaccines, Synthetic / therapeutic use*
Vaccinia virus / immunology*
Grant Support
11647//Cancer Research UK; //Cancer Research UK
Reg. No./Substance:
0/Antigens, Viral; 0/Cancer Vaccines; 0/Vaccines, Synthetic

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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