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 ORCID: https://orcid.org/0000-0002-9856-2938, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, 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:	04 May 2023 17:06
URI:	https://orca.cardiff.ac.uk/id/eprint/79532

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