| 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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Selective Laser Trabeculoplasty for the Management of Open-Angle Glaucoma in St. Lucia.
Next Document: Pirfenidone Inhibits Pancreatic Cancer Desmoplasia by Regulating Stellate Cells.