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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.

Original publication

DOI

10.1002/ijc.20569

Type

Journal article

Journal

Int J Cancer

Publication Date

10/01/2005

Volume

113

Pages

259 - 266

Keywords

Adult, Aged, Antibody Formation, Antigens, Neoplasm, Enzyme-Linked Immunosorbent Assay, Epitopes, Female, Genetic Engineering, Humans, Immunotherapy, Male, Melanoma, Middle Aged, Neoplasm Recurrence, Local, Plasmids, Skin Neoplasms, T-Lymphocytes, Cytotoxic, Vaccines, DNA, Vaccines, Synthetic, Vaccinia virus