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Recombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence
Author(s) -
Smith Caroline L.,
Dunbar P. Rod,
Mirza Fareed,
Palmowski Michael J.,
Shepherd Dawn,
Gilbert Sarah C.,
Coulie Pierre,
Schneider Joerg,
Hoffman Eric,
Hawkins Robert,
Harris Adrian L.,
Cerundolo Vincenzo
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20569
Subject(s) - ctl* , epitope , elispot , virology , vaccinia , cytotoxic t cell , recombinant dna , antigen , biology , modified vaccinia ankara , immunology , cd8 , in vitro , biochemistry , gene
Recombinant plasmid DNA and attenuated poxviruses are under development as cancer and infectious disease vaccines. We present the results of a phase I clinical trial of recombinant plasmid DNA and modified vaccinia Ankara (MVA), both encoding 7 melanoma tumor antigen cytotoxic T lymphocyte (CTL) epitopes. HLA‐A*0201‐positive patients with surgically treated melanoma received either a “prime‐boost” DNA/MVA or a homologous MVA‐only regimen. Ex vivo tetramer analysis, performed at multiple time points, provided detailed kinetics of vaccine‐driven CTL responses specific for the high‐affinity melan‐A26, 27, 28, 29, 30, 31, 32, 33, 34, 35 analogue epitope. Melan‐A26‐35‐specific CTL were generated in 2/6 patients who received DNA/MVA (detectable only after the first MVA injection) and 4/7 patients who received MVA only. Ex vivo ELISPOT analysis and in vitro proliferation assays confirmed the effector function of these CTL. Responses were seen in smallpox‐vaccinated as well as vaccinia‐naïve patients, as defined by anti‐vaccinia antibody responses demonstrated by ELISA assay. The observations that 1) CTL responses were generated to only 1 of the recombinant epitopes and 2) that the magnitude of these responses (0.029–0.19% CD8 + T cells) was below the levels usually seen in acute viral infections suggest that to ensure high numbers of CTL specific for multiple recombinant epitopes, a deeper understanding of the interplay between CTL responses specific for the viral vector and recombinant epitopes is required.