Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients.
Epstein-Barr virus (EBV) is associated with several malignancies including nasopharyngeal carcinoma, a high incidence tumor in Chinese populations, in which tumor cells express the two EBV antigens EB nuclear antigen 1 (EBNA1) and latent membrane protein 2 (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 patients with nasopharyngeal carcinoma to determine a safe and immunogenic dose. The patients, all in remission more than 12 weeks after primary therapy, received three intradermal MVA-EL vaccinations at three weekly intervals, using five escalating dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming unit (pfu). Blood samples were taken during prescreening, immediately before vaccination, one week afterward and at intervals up to one year later. Immunogenicity was tested by IFN-γ 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 one to four and six at the highest dose, without dose-limiting toxicity. T-cell responses to one or both vaccine antigens were increased in 15 of 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 six 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.
Department of Clinical Oncology, State Key Laboratory in Oncology in South China, Sir YK Pao Center for Cancer, Hong Kong Cancer Institute and Li Ka Shing Institute for Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.
Edwin P
EP
Hui
Graham S
GS
Taylor
Hui
H
Jia
Brigette B Y
BB
Ma
Stephen L
SL
Chan
Rosalie
R
Ho
Wai-Lap
WL
Wong
Steven
S
Wilson
Benjamin F
BF
Johnson
Ceri
C
Edwards
Deborah D
DD
Stocken
Alan B
AB
Rickinson
Neil M
NM
Steven
Anthony T C
AT
Chan
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*; D014614:Vaccines, Synthetic / Q000627:therapeutic use*; D014616:Vaccinia virus / Q000276:immunology*
D000956:Antigens, Viral; D019496:Cancer Vaccines; D014614:Vaccines, Synthetic