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Establishment of shared antigen reactive cytotoxic T lymphocyte using co-stimulatory molecule introduced autologous cancer cells
Authors:Yoshihiko Hirohashi  Toshihiko Torigoe  Yasuaki Tamura  Yuuji Inoue  Kenjiro Kamiguchi  Aya Sasaki  Noriyuki Sato
Institution:a Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, chuo-ku, Sapporo 060-8556, Japan
b Department of Otolaryngology, Wakayama Medical University, Kimiidera 811-1, Wakayama 641-8509, Japan
c Sapporo Respiratory Medicine Hospital, Sakae-dori 3 chou-me, Shiroishi-ku, Sapporo 003-0021, Japan
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.
Keywords:CTLs  cytotoxic T lymphocytes  TAAs  tumor-associated antigens  APC  antigen-presenting cell  PBMC  peripheral blood mononuclear cell  MLTC  mixed lymphocyte tumor cell culture  TILs  tumor infiltrating lymphocytes  mAb  monoclonal antibody  FCM  flowcytometer
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