Human tumor-derived genomic DNA transduced into a recipient cell induces tumor-specific immune responses ex vivo.
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.
Whiteside
Theresa L
TL
Department of Pathology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. whitesidetl@msx.upmc.edu
Gambotto
Andrea
A
Albers
Andreas
A
Stanson
Joanna
J
Cohen
Edward P
EP
D017951:Antigen Presentation; D017209:Apoptosis; D019496:Cancer Vaccines / Q000235:genetics*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000235:genetics; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008164:Luminescent Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000235:genetics*; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; D004273:DNA, Neoplasm; D000939:Epitopes; D015789:HLA-A2 Antigen; D007376:Interleukin-2; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D019444:Vaccines, DNA; D058951:gp100 Melanoma Antigen; D049452:Green Fluorescent Proteins