A phase I vaccination study with tyrosinase in patients with stage II melanoma using recombinant modified vaccinia virus Ankara (MVA-hTyr)

Details

Serval ID
serval:BIB_991634A39465
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A phase I vaccination study with tyrosinase in patients with stage II melanoma using recombinant modified vaccinia virus Ankara (MVA-hTyr)
Journal
Cancer Immunology Immunotherapy
Author(s)
Meyer  R. G., Britten  C. M., Siepmann  U., Petzold  B., Sagban  T. A., Lehr  H. A., Weigle  B., Schmitz  M., Mateo  L., Schmidt  B., Bernhard  H., Jakob  T., Hein  R., Schuler  G., Schuler-Thurner  B., Wagner  S. N., Drexler  I., Sutter  G., Arndtz  N., Chaplin  P., Metz  J., Enk  A., Huber  C., Wolfel  T.
ISSN
0340-7004 (Print)
Publication state
Published
Issued date
2005
Volume
54
Number
5
Pages
453-467
Notes
PT - Clinical Trial PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't
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
Keywords
Adult/Aged/Antibodies/blood/Antibody Formation/CD4-Positive T-Lymphocytes/immunology/CD8-Positive T-Lymphocytes/Cancer Vaccines/genetics/DNA,Complementary/Dendritic Cells/transplantation/Genetic Vectors/HLA-A Antigens/Humans/Male/Melanoma/therapy/Middle Aged/Monophenol Monooxygenase/Neoplasm Staging/RNA,Messenger/Transfection/Vaccinia virus
Pubmed
Web of science
Create date
29/01/2008 18:36
Last modification date
20/08/2019 15:00
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