Establishment of shared antigen reactive cytotoxic T lymphocyte using co-stimulatory molecule introduced autologous cancer cells.

Abstract

Cytotoxic T lymphocytes (CTLs) play an essential role in immunological responses for tumor rejection. In the past decade, many tumor-associated antigens (TAAs) have been identified predominantly in melanomas. Several clinical trials based on such antigenic peptides with or without adjuvants brought about partially favorable results, suggesting that identification of more immunogenic TAAs is needed. We show here the successful establishment of human leukocyte antigen (HLA)-A24-restricted CTL (TcLHK2 line1) from a pleural effusion of lung cancer patient, using B7.1 (CD80) transduced autologous lung cancer cells as an antigen-presenting cell (APC). TcLHK2 line1 recognized autologous lung adenocarcinoma cell line LHK2 in an HLA-A24-restricted fashion. Moreover, this CTL line also recognized allogeneic HLA-A24-positive lung adenocarcinoma cell line, gastric carcinoma cell line and melanoma cell line. These data raise the possibility that co-stimulatory molecule B7.1 (CD80) plays important role to overcome the immunological tolerance. Furthermore, TcLHK2 line1 is a useful tool for the identification of widely expressed shared antigens restricted by HLA-A24. Further analysis of this CTL and autologous cancer cell line will bring about novel TAAs.

• Authors: Yoshihiko Hirohashi, Toshihiko Torigoe, Itaru Hirai, Yasuaki Tamura, Munehide Nakatsugawa, Yuuji Inoue, Takayuki Kanaseki, Kenjiro Kamiguchi, Hideyuki Ikeda, Aya Sasaki, Noboru Yamanaka, Noriyuki Sato
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 88 Issue 1 Pg. 128-32 (Feb 2010) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 19818766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Neoplasm
• B7-1 Antigen
• Epitopes
• HLA-A Antigens
• HLA-A24 Antigen

Topics

• Adenocarcinoma (immunology, pathology)
• Aged
• Antigen-Presenting Cells
• Antigens, Neoplasm (immunology)
• B7-1 Antigen (immunology)
• Cell Line, Tumor
• Cytotoxicity, Immunologic (immunology)
• Epitopes (immunology)
• HLA-A Antigens (immunology)
• HLA-A24 Antigen
• Humans
• Immune Tolerance
• Lung Neoplasms (immunology, pathology)
• Male
• Melanoma (immunology, pathology)
• Stomach Neoplasms (immunology, pathology)
• T-Lymphocytes, Cytotoxic (cytology, immunology)