title: A phase I vaccination study with tyrosinase in patients with stage II melanoma using recombinant modified vaccinia virus Ankara (MVA-hTyr).
abstract: A significant percentage of patients with stage II melanomas suffer a relapse after surgery and therefore need the development of adjuvant therapies. In the study reported here, safety and immunological response were analyzed after vaccination in an adjuvant setting with recombinant modified vaccinia virus Ankara carrying the cDNA for human tyrosinase (MVA-hTyr). A total of 20 patients were included and vaccinated three times at 4-week intervals with 5x10(8) IU of MVA-hTyr each time. The responses to the viral vector, to known HLA class I-restricted tyrosinase peptides, and to dendritic cells transfected with tyrosinase mRNA, were investigated by ELISpot assay on both ex vivo T cells and on T cells stimulated in vitro prior to testing. The delivery of MVA-hTyr was safe and did not cause any side effects above grade 2. A strong response to the viral vector was achieved, indicated by an increase in the frequency of MVA-specific CD4+ and CD8+ T cells and an increase in virus-specific antibody titers. However, no tyrosinase-specific T-cell or antibody response was observed with MVA-hTyr in any of the vaccinated patients. Although MVA-hTyr provides a safe and effective antigen-delivery system, it does not elicit a measurable immune response to its transgene product in patients with stage II melanoma after repeated combined intradermal and subcutaneous vaccination. We presume that modification of the antigen and/or prime-boost vaccination applying different approaches to antigen delivery may be required to induce an effective tyrosinase-specific immune response.
authors.affiliation: III. Medizinische Klinik, Johannes Gutenberg-Universitaet, Langenbeckstrasse 1, 55116 Mainz, Germany.
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Meyer
authors.forename: Cedrik M
authors.initials: CM
authors.lastname: Britten
authors.forename: Ulrike
authors.initials: U
authors.lastname: Siepmann
authors.forename: Barbara
authors.initials: B
authors.lastname: Petzold
authors.forename: Tolga A
authors.initials: TA
authors.lastname: Sagban
authors.forename: Hans A
authors.initials: HA
authors.lastname: Lehr
authors.forename: Bernd
authors.initials: B
authors.lastname: Weigle
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: Luis
authors.initials: L
authors.lastname: Mateo
authors.forename: Burkhard
authors.initials: B
authors.lastname: Schmidt
authors.forename: Helga
authors.initials: H
authors.lastname: Bernhard
authors.forename: Thilo
authors.initials: T
authors.lastname: Jakob
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hein
authors.forename: Gerold
authors.initials: G
authors.lastname: Schuler
authors.forename: Beatrice
authors.initials: B
authors.lastname: Schuler-Thurner
authors.forename: Stephan N
authors.initials: SN
authors.lastname: Wagner
authors.forename: Ingo
authors.initials: I
authors.lastname: Drexler
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
authors.forename: Nathaly
authors.initials: N
authors.lastname: Arndtz
authors.forename: Paul
authors.initials: P
authors.lastname: Chaplin
authors.forename: Jost
authors.initials: J
authors.lastname: Metz
authors.forename: Alexander
authors.initials: A
authors.lastname: Enk
authors.forename: Christoph
authors.initials: C
authors.lastname: Huber
authors.forename: Thomas
authors.initials: T
authors.lastname: Wölfel
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D003713:Dendritic Cells / Q000637:transplantation; D005822:Genetic Vectors / Q000235:genetics; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics* / Q000276:immunology*; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D018076:DNA, Complementary; D015234:HLA-A Antigens; D012333:RNA, Messenger; D014442:Monophenol Monooxygenase