Recognition of Epstein-Barr virus-associated gastric carcinoma cells by cytotoxic T lymphocytes induced in vitro with autologous lymphoblastoid cell line and LMP2-derived, HLA-A24-restricted 9-mer peptide

  • Authors:
    • Kaori Okugawa
    • Tsuyoshi Itoh
    • Ichiro Kawashima
    • Kazutoh Takesako
    • Osam Mazda
    • Ikuei Nukaya
    • Yutaro Yano
    • Yoshiki Yamamoto
    • Hisakazu Yamagishi
    • Yuji Ueda
  • View Affiliations

  • Published online on: October 1, 2004     https://doi.org/10.3892/or.12.4.725
  • Pages: 725-731
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Epstein-Barr virus (EBV) is associated with several types of malignancies including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and gastric carcinoma. Previous reports have suggested that EBV-related antigen-targeting immunotherapy is one of the promising approaches for the treatment of these malignancies other than gastric carcinoma. EBV-associated gastric carcinoma (EBVaGC) has been shown to express Epstein-Barr virus nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). In the present study, DNA and mRNA freshly isolated from tumors of patients with gastric cancer were subjected to polymerase chain reaction (PCR) using EBV-specific primers and reverse transcription (RT)-PCR specific for LMP2 transcripts. EBV-specific region was identified in genomic DNA isolated from cancerous tissues in 22% of gastric cancer patients. LMP2 mRNA was also detected in 3 out of these 5 DNA positive samples tested. To investigate the feasibility of specific immunotherapy for EBVaGC, we induced cytotoxic T lymphocytes (CTLs) from peripheral blood lymphocytes using two kinds of antigen-presenting cells (APCs) such as autologous lymphoblastoid cell line (LCL) and LMP2-derived peptide-pulsed dendritic cells (DCs). The cytotoxicity of these CTLs against peptide-pulsed targets was examined by standard 51Cr release assay and interferon (IFN)-γ production assay. We further assessed the recognition of tumor cells endogenously expressing LMP2 by these T cells. T cells induced by peptide-loaded DCs and autologous LCL efficiently lysed peptide-pulsed targets. Furthermore, these T cells could recognize not only tumor cells transfected with LMP2, but also LMP2-positive gastric cancer cells which were successfully isolated and cultured from specimens obtained by surgery. Collectively, sensitization of peripheral blood lymphocytes with LMP2-derived peptide was able to induce CTL response against EBVaGC cells. Thus, EBVaGC is susceptible for the LMP2-targeting immunotherapy.

Related Articles

Journal Cover

October 2004
Volume 12 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Okugawa K, Itoh T, Kawashima I, Takesako K, Mazda O, Nukaya I, Yano Y, Yamamoto Y, Yamagishi H, Ueda Y, Ueda Y, et al: Recognition of Epstein-Barr virus-associated gastric carcinoma cells by cytotoxic T lymphocytes induced in vitro with autologous lymphoblastoid cell line and LMP2-derived, HLA-A24-restricted 9-mer peptide. Oncol Rep 12: 725-731, 2004
APA
Okugawa, K., Itoh, T., Kawashima, I., Takesako, K., Mazda, O., Nukaya, I. ... Ueda, Y. (2004). Recognition of Epstein-Barr virus-associated gastric carcinoma cells by cytotoxic T lymphocytes induced in vitro with autologous lymphoblastoid cell line and LMP2-derived, HLA-A24-restricted 9-mer peptide. Oncology Reports, 12, 725-731. https://doi.org/10.3892/or.12.4.725
MLA
Okugawa, K., Itoh, T., Kawashima, I., Takesako, K., Mazda, O., Nukaya, I., Yano, Y., Yamamoto, Y., Yamagishi, H., Ueda, Y."Recognition of Epstein-Barr virus-associated gastric carcinoma cells by cytotoxic T lymphocytes induced in vitro with autologous lymphoblastoid cell line and LMP2-derived, HLA-A24-restricted 9-mer peptide". Oncology Reports 12.4 (2004): 725-731.
Chicago
Okugawa, K., Itoh, T., Kawashima, I., Takesako, K., Mazda, O., Nukaya, I., Yano, Y., Yamamoto, Y., Yamagishi, H., Ueda, Y."Recognition of Epstein-Barr virus-associated gastric carcinoma cells by cytotoxic T lymphocytes induced in vitro with autologous lymphoblastoid cell line and LMP2-derived, HLA-A24-restricted 9-mer peptide". Oncology Reports 12, no. 4 (2004): 725-731. https://doi.org/10.3892/or.12.4.725