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

Shinji Kondo, Ayako Demachi-Okamura, Tomoya Hirosawa, Hiroyuki Maki, Mitsugu Fujita, Yasushi Uemura, Yoshiki Akatsuka, Eiko Yamamoto, Kiyosumi Shibata, Kazuhiko Ino, Fumitaka Kikkawa, Kiyotaka Kuzushima

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1103-1110
Number of pages8
JournalHuman Immunology
Volume74
Issue number9
DOIs
Publication statusPublished - 01-09-2013

Fingerprint

Claudin-1
Cytotoxic T-Lymphocytes
Ovarian Neoplasms
Epitopes
Cell Line
Clone Cells
Autoantigens
Gene Silencing
Antigen-Presenting Cells
RNA Interference
Gene Library
Organism Cloning
Epithelial Cells
Alleles
Tissue Donors
Carcinoma
T-Lymphocytes
Antigens
Messenger RNA
Peptides

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kondo, Shinji ; Demachi-Okamura, Ayako ; Hirosawa, Tomoya ; Maki, Hiroyuki ; Fujita, Mitsugu ; Uemura, Yasushi ; Akatsuka, Yoshiki ; Yamamoto, Eiko ; Shibata, Kiyosumi ; Ino, Kazuhiko ; Kikkawa, Fumitaka ; Kuzushima, Kiyotaka. / 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. In: Human Immunology. 2013 ; Vol. 74, No. 9. pp. 1103-1110.
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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. Na{\"i}ve 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.",
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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 2013, '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', Human Immunology, vol. 74, no. 9, pp. 1103-1110. https://doi.org/10.1016/j.humimm.2013.06.030

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. / Kondo, Shinji; Demachi-Okamura, Ayako; Hirosawa, Tomoya; Maki, Hiroyuki; Fujita, Mitsugu; Uemura, Yasushi; Akatsuka, Yoshiki; Yamamoto, Eiko; Shibata, Kiyosumi; Ino, Kazuhiko; Kikkawa, Fumitaka; Kuzushima, Kiyotaka.

In: Human Immunology, Vol. 74, No. 9, 01.09.2013, p. 1103-1110.

Research output: Contribution to journalArticle

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T1 - 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

AU - Kondo, Shinji

AU - Demachi-Okamura, Ayako

AU - Hirosawa, Tomoya

AU - Maki, Hiroyuki

AU - Fujita, Mitsugu

AU - Uemura, Yasushi

AU - Akatsuka, Yoshiki

AU - Yamamoto, Eiko

AU - Shibata, Kiyosumi

AU - Ino, Kazuhiko

AU - Kikkawa, Fumitaka

AU - Kuzushima, Kiyotaka

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Y1 - 2013/9/1

N2 - 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.

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