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.
Smith, Caroline L Dunbar, P Rod Mirza, Fareed Palmowski, Michael J Shepherd, Dawn Gilbert, Sarah C Coulie, Pierre Schneider, Joerg Hoffman, Eric Hawkins, Robert E
Smith, Caroline L
Dunbar, P Rod
Mirza, Fareed
Palmowski, Michael J
Shepherd, Dawn
Gilbert, Sarah C
Coulie, Pierre
Schneider, Joerg
Hoffman, Eric
Hawkins, Robert E
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Abstract
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-A(26-35) 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-naive 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.
Description
Date
2005-01-10
Publisher
Collections
Keywords
Cancer Recurrence
Skin Cancer
Skin Cancer
Type
Article
Citation
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. 2005, 113 (2):259-66 Int. J. Cancer