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A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer.


ABSTRACT: PURPOSE:Epstein-Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumor antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses. EXPERIMENTAL DESIGN:Sixteen patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma (NPC) received three intradermal vaccinations of MVA-EL at 3-weekly intervals at dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming units (pfu). Blood samples were taken at screening, after each vaccine cycle, and during the post-vaccination period. T-cell responses were measured using IFN? ELISpot assays with overlapping EBNA1/LMP2 peptide mixes or HLA-matched epitope peptides. Polychromatic flow cytometry was used to characterize functionally responsive T-cell populations. RESULTS:Vaccination was generally well tolerated. Immunity increased after vaccination to at least one antigen in 8 of 14 patients (7/14, EBNA1; 6/14, LMP2), including recognition of epitopes that vary between EBV strains associated with different ethnic groups. Immunophenotypic analysis revealed that vaccination induced differentiation and functional diversification of responsive T-cell populations specific for EBNA1 and LMP2 within the CD4 and CD8 compartments, respectively. CONCLUSIONS:MVA-EL is safe and immunogenic across diverse ethnicities and thus suitable for use in trials against different EBV-positive cancers globally as well as in South-East Asia where NPC is most common. The highest dose (5 × 10(8) pfu) is recommended for investigation in current phase IB and II trials.

SUBMITTER: Taylor GS 

PROVIDER: S-EPMC4340506 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer.

Taylor Graham S GS   Jia Hui H   Harrington Kevin K   Lee Lip Wai LW   Turner James J   Ladell Kristin K   Price David A DA   Tanday Manjit M   Matthews Jen J   Roberts Claudia C   Edwards Ceri C   McGuigan Lesley L   Hartley Andrew A   Wilson Steve S   Hui Edwin P EP   Chan Anthony T C AT   Rickinson Alan B AB   Steven Neil M NM  

Clinical cancer research : an official journal of the American Association for Cancer Research 20140814 19


<h4>Purpose</h4>Epstein-Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumor antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses.<h4>Experimental design</h4>Sixteen patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma (NPC) recei  ...[more]

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