RRC ID 34738
Author Kondo S, Demachi-Okamura A, Hirosawa T, Maki H, Fujita M, Uemura Y, Akatsuka Y, Yamamoto E, Shibata K, Ino K, Kikkawa F, Kuzushima K.
Title An HLA-modified ovarian cancer cell line induced CTL responses specific to an epitope derived from claudin-1 presented by HLA-A*24:02 molecules.
Journal Hum. Immunol.
Abstract In an attempt to induce cytotoxic T lymphocytes (CTLs) that react to ovarian cancer cells, we isolated a CTL clone that specifically recognizes claudin-1 in an HLA-A*24:02-restricted manner. Naïve CD8(+) T lymphocytes were obtained from a healthy adult donor and stimulated twice in vitro with HLA-modified TOV21G cells that were originally derived from an ovarian clear-cell carcinoma line. The TOV21G modification involved RNAi-mediated gene silencing of intrinsic HLA molecules and lentiviral transduction of a synonymously mutated HLA-A*24:02. Then, cDNA library construction using mRNA extracted from the parental TOV21G cells and subsequent expression cloning were conducted. These experiments revealed that a CTL clone obtained from the bulk culture recognized a minimal epitope peptide RYEFGQALF, which was derived from an autoantigen claudin-1 presented by HLA-A*24:02 molecules. This clone exhibited cytolytic activities against three ovarian cancer cell lines and normal bronchial epithelial cells in an HLA-A*24:02-restricted manner. Our data indicate that HLA-modified cancer cells can be used as an artificial antigen-presenting cell to generate antigen-specific CTLs in a manner restricted by an HLA allele of interest.
Volume 74(9)
Pages 1103-10
Published 2013-9
DOI 10.1016/j.humimm.2013.06.030
PII S0198-8859(13)00187-0
PMID 23806269
MeSH Adenocarcinoma, Clear Cell / immunology* Adult Cell Line, Tumor Claudin-1 / immunology Claudin-1 / metabolism* Clone Cells Cytotoxicity, Immunologic Epitopes, T-Lymphocyte / immunology Epitopes, T-Lymphocyte / metabolism* Female HLA-A24 Antigen / genetics HLA-A24 Antigen / metabolism* Humans Lymphocyte Activation Ovarian Neoplasms / immunology* Peptide Fragments / immunology Peptide Fragments / metabolism* Respiratory Mucosa / immunology T-Lymphocytes, Cytotoxic / immunology* Transgenes / genetics
IF 1.994
Times Cited 3
DNA material CSII-EF-MCS (RDB04378)