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Phase 1 trial of recombinant Modified Vaccinia Ankara (MVA) encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients.
MedLine Citation:
PMID:  23348421     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Epstein-Barr virus (EBV) is associated with several malignancies including nasopharyngeal carcinoma (NPC), a high incidence tumor in Chinese populations, in which tumor cells express the two EBV antigens EBNA1 and 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 NPC patients to determine a safe and immunogenic dose. The patients, all in remission >12 weeks after primary therapy, received 3 intradermal MVA-EL vaccinations at 3 weekly intervals, using 5 escalating dose levels between 5x10^7 and 5x10^8 pfu. Blood samples were taken during pre-screening, immediately before vaccination, 1 week afterward and at intervals up to one year later. Immunogenicity was tested by interferon-gamma 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 1-4 and six at the highest dose, without dose-limiting toxicity. T cell responses to one or both vaccine antigens were increased in 15/18 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 6 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.
Authors:
Edwin P Hui; Graham S Taylor; Hui Jia; Brigette By Ma; Stephen L Chan; Rosalie Ho; Wl Wong; Steven Wilson; Benjamin F Johnson; Ceri Edwards; Deborah D Stocken; Alan B Rickinson; Neil M Steven; Anthony T C Chan
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Clinical Oncology, The Chinese University of Hong Kong.
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