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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Stanson, Joanna Whiteside, Theresa L. Albers, Andreas Gambotto, Andrea Cohen, Edward P. |
| Description | Author Affiliation: Whiteside TL ( Department of Pathology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. whitesidetl@msx.upmc.edu); |
| Abstract | This article describes a DNA-based vaccination strategy evaluated ex vivo with human cells. The vaccine was prepared by transferring tumor-derived genomic DNA to PCI-13 cells, a highly immunogenic tumor cell line ('recipient cell'), which had been genetically modified to secrete IL-2 (PCI-13/IL-2). PCI-13 cells expressed class I MHC determinants (HLA-A2) shared with the tumor from which the DNA was obtained as well as allogeneic determinants. DNA from a gp100(+) melanoma cell line was transduced into gp100(-) PCI-13/IL-2 cells (PCI-13/IL-2/DNA). A T cell line specific for the gp100 epitope responded to PCI-13/IL-2/DNA cells by IFN-gamma-secretion measured in enzyme-linked immunospot assays. The T cell line also recognized the gp100 epitope presented by dendritic cells that ingested PCI-13/IL-2/DNA cells, which had been induced by UVB irradiation to undergo apoptosis. After up-take and processing of apoptotic PCI-13/IL-2/DNA cells, the dendritic cells primed normal peripheral blood lymphocytes to generate effector T cells specific for the tumor donating the DNA. The results indicate that tumor epitopes encoded in such DNA are expressed in recipient cells and can induce tumor-specific T cells. The findings support translation of this vaccination strategy to a phase I trial in patients with cancer. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 14 |
| Volume Number | 99 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2002-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cancer Vaccines Genetics DNA, Neoplasm Vaccines, DNA Antigen Presentation Apoptosis Cell Line Dendritic Cells Immunology Epitopes Gene Expression Genes, Reporter Green Fluorescent Proteins HLA-A2 Antigen Metabolism In Vitro Techniques Interleukin-2 Biosynthesis Luminescent Proteins Membrane Glycoproteins Neoplasm Proteins T-Lymphocytes Transduction, Genetic Tumor Cells, Cultured Gp100 Melanoma Antigen Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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