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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/75657
Title:
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.
Authors:
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; Harris, Adrian L; Cerundolo, Vincenzo
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.
Affiliation:
Tumour Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, OX3 9DS, UK.
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
Journal:
International Journal of Cancer
Issue Date:
10-Jan-2005
URI:
http://hdl.handle.net/10541/75657
DOI:
10.1002/ijc.20569
PubMed ID:
15386406
Type:
Article
Language:
en
ISSN:
0020-7136
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
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.en
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

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.