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dc.contributor.authorSmith, Caroline L
dc.contributor.authorDunbar, P Rod
dc.contributor.authorMirza, Fareed
dc.contributor.authorPalmowski, Michael J
dc.contributor.authorShepherd, Dawn
dc.contributor.authorGilbert, Sarah C
dc.contributor.authorCoulie, Pierre
dc.contributor.authorSchneider, Joerg
dc.contributor.authorHoffman, Eric
dc.contributor.authorHawkins, Robert E
dc.contributor.authorHarris, Adrian L
dc.contributor.authorCerundolo, Vincenzo
dc.date.accessioned2009-07-24T15:31:48Z
dc.date.available2009-07-24T15:31:48Z
dc.date.issued2005-01-10
dc.identifier.citationRecombinant 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. Canceren
dc.identifier.issn0020-7136
dc.identifier.pmid15386406
dc.identifier.doi10.1002/ijc.20569
dc.identifier.urihttp://hdl.handle.net/10541/75657
dc.description.abstractRecombinant 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.
dc.language.isoenen
dc.subjectCancer Recurrenceen
dc.subjectSkin Canceren
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAntibody Formation
dc.subject.meshAntigens, Neoplasm
dc.subject.meshEnzyme-Linked Immunosorbent Assay
dc.subject.meshEpitopes
dc.subject.meshFemale
dc.subject.meshGenetic Engineering
dc.subject.meshHumans
dc.subject.meshImmunotherapy
dc.subject.meshMale
dc.subject.meshMelanoma
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Recurrence, Local
dc.subject.meshPlasmids
dc.subject.meshSkin Neoplasms
dc.subject.meshT-Lymphocytes, Cytotoxic
dc.subject.meshVaccines, DNA
dc.subject.meshVaccines, Synthetic
dc.subject.meshVaccinia virus
dc.titleRecombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence.en
dc.typeArticleen
dc.contributor.departmentTumour Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, OX3 9DS, UK.en
dc.identifier.journalInternational Journal of Canceren
html.description.abstractRecombinant 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.


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