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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., Jia, Hui, Harrington, Kevin, Lee, Lip Wai, Turner, James, Ladell, Kristin, Price, David, Tanday, Manjit, Matthews, Jen, Roberts, Claudia, Edwards, Ceri, McGuigan, Lesley, Hartley, Andrew, Wilson, Steve, Hui, Edwin P., Chan, Anthony T.C., Rickinson, Alan B. and Steven, Neil M. 2014. A recombinant modified vaccinia Ankara vaccine encoding Epstein-Barr virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer. Clinical Cancer Research 20 (19) , pp. 5009-5022. 10.1158/1078-0432.CCR-14-1122-T

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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 × 107 and 5 × 108 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 IFNγ 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 × 108 pfu) is recommended for investigation in current phase IB and II trials. Clin Cancer Res; 20(19); 5009–22. ©2014 AACR.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: American Association for Cancer Research
ISSN: 1078-0432
Date of First Compliant Deposit: 6 September 2017
Date of Acceptance: 21 July 2014
Last Modified: 07 Feb 2019 10:53
URI: http://orca.cf.ac.uk/id/eprint/79532

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