|Title:||Identification of HLA-A11-restricted CTL epitopes derived from HPV type 18 using DNA immunization||Authors:||Chen H.-W.
|Keywords:||Cervical cancer; Cytotoxic T lymphocytes; HLA-A11; HPV18; Peptide-based vaccine||Issue Date:||2009||Journal Volume:||8||Journal Issue:||21||Start page/Pages:||2025-2032||Source:||Cancer Biology and Therapy||Abstract:||
Identification of the cytotoxic T lymphocyte (CTL) epitopes of tumor antigens is important for effective immunotherapy. We report that a combination of epitope prediction, enzyme-linked immunosorbent assay (ELISA)-based epitope-HLA complex formation, and DNA immunization methods can improve the efficiency and accuracy of CTL epitope studies. In this study, two HLA-A11-restricted epitopes derived from human papillomavirus (HPV)18 E6 oncoprotein were identified. HLA-A11-transgenic mice immunized with these epitopes could specifically induce interferon-? (IFN?) production, cytotoxicity and peptide/HLA-A11 tetramer binding in CD8+ T-cells. To study intracellular processing of CTL epitopes, we constructed a DNA plasmid containing an endoplasmic reticulum (ER) targeting sequence as well as the HPV18 E6 and E7 genes (pEK/HPV18E6E7). CTL responses against peptide-pulsed T2/A11 cells could be detected after immunizing HLA-A11-transgenic mice with pEK/HPV18E6E7. Furthermore, the identified peptides could stimulate T-cells to secrete IFN? from HPV18-infected patients. Our results demonstrate that the antigenic E6 peptides derived from HPV18 are potential candidates for the treatment of HPV 18-associated tumors in HLA-A11+ populations. ? 2009 Landes Bioscience.
|ISSN:||1538-4047||DOI:||10.4161/cbt.8.21.9732||SDG/Keyword:||epitope; gamma interferon; HLA A11 antigen; human papillomavirus 18 e6 oncoprotein; plasmid DNA; plasmid vector; recombinant protein; tetramer; tumor antigen; unclassified drug; animal cell; animal cell culture; animal experiment; article; blood sampling; CD8+ T lymphocyte; cytokine production; cytotoxic T lymphocyte; cytotoxicity; DNA immunization; endoplasmic reticulum; enzyme linked immunosorbent assay; Human papillomavirus type 18; mouse; nonhuman; plasmid; polymerase chain reaction; protein expression; spleen cell; transgenic mouse; uterine cervix cancer
|Appears in Collections:||醫學系|
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