更新于：2024-11-01

KKLC1 x HLA class I抗原

更新于：2024-11-01

基本信息

关联

项与 KKLC1 x HLA class I抗原相关的药物

821-TCR

靶点

HLA class I抗原 x KKLC1

作用机制

HLA class I抗原调节剂 [+1]

在研机构

T-Cure Bioscience, Inc.初创企业

原研机构

T-Cure Bioscience, Inc.初创企业

在研适应症

实体瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 KKLC1 x HLA class I抗原相关的临床结果

登录后查看更多信息

100 项与 KKLC1 x HLA class I抗原相关的转化医学

登录后查看更多信息

0 项与 KKLC1 x HLA class I抗原相关的专利（医药）

登录后查看更多信息

项与 KKLC1 x HLA class I抗原相关的文献（医药）

2020-11-01·Cancer Science2区 · 医学

Development of adoptive immunotherapy with KK‐LC‐1‐specific TCR‐transduced γδT cells against lung cancer cells

2区 · 医学

ArticleOA

作者: Takenoyama, Mitsuhiro ; Yasumoto, Kosei ; So, Tetsuya ; Baba, Tetsuro ; Shigematsu, Yoshiki ; Ichiki, Yoshinobu ; Shiota, Hironobu ; Fukuyama, Takashi ; Nagata, Yoshika ; Yasuda, Manabu

AbstractThe present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐specific CTLs to establish forceful cancer‐specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA‐B15 restricted recognition of Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL‐2. The KK‐LC‐1‐specific TCRαβ‐CD8 γδT cells showed cytotoxic activity against the KK‐LC‐1 positive lung cancer cell line F1121L and produced IFN‐γ against F1121L and KK‐LC‐1 peptide‐pulsed F1121 EBV‐B cells. These responses were blocked by HLA class I and HLA‐B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells (TCRαβ‐CD8 γδT cells) were intravenously injected. Growth inhibition of KK‐LC‐1+, HLA‐B15+ lung cancer cells was confirmed in mice with injection of the TCRαβ‐CD8 γδT cells from 1 wk after xenotransplantation of cancer cells but not in those treated 2 wk after xenotransplantation. The resected specimens of the tumor, 2 wk after xenotransplantation, highly expressed FasL but not programmed death ligand‐1 (PD‐L1) by immunohistochemical staining. FasL highly expressed cancer cells xenotransplanted 2 wk ago were resistant to TCRαβ‐CD8 γδT cells injection. These results suggested that apoptosis of Fas‐positive TCRαβ‐CD8 γδT cells may be induced by a Fas‐mediated signal after interacting with FasL‐positive cancer cells.

2013-05-01·Anticancer research

Clinical significance of expression of cancer/testis antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer.

Article

作者: Takenaka, Masaru ; Uramoto, Hidetaka ; Baba, Tetsuro ; Yamada, Sohsuke ; So, Tomoko ; Oka, Sohich ; Shinohara, Shinji ; Hanagiri, Takeshi ; Nagata, Yoshika ; Shigematsu, Yoshiki ; Chikaishi, Yasuhiro

AIMThe purpose of this study was to investigate the clinical significance of expression of cancer/testis (CT) antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer (NSCLC), which underwent complete surgical resection.PATIENTS AND METHODSThe expression of HLA class-I molecules was evaluated in 136 resected NSCLC specimens by immunohistochemistry. The results were scored as the percentage of stained tumor cells and categorized into two groups: 0-79%, reduced expression; and >80%, normal expression. The expression of CT antigen was performed by reverse transcription-polymerase chain reaction (RT-PCR).RESULTSThe expression of HLA class-I was normal in 49 tumors (36%), and there was reduced expression in 87 tumors (64%). The expression of Melanoma antigen (MAGE)-A3, MAGE-A4, and Kita-Kyushu lung cancer antigen-1 (KK-LC-1) was positive in 34 (25.0%), 22 (16.2%), and 42 (30.9%) patients, respectively. There was no significant difference in the proportion of HLA class-I expression associated with the expression of any of the CT antigens. Among the patients with positive expression of at least one of the CT antigens, the 5-year survival rate of the patients with the normal expression of HLA class-I was 87.5%; however, it was 63.4% in patients with the reduced expression of HLA class-I (p=0.0477).CONCLUSIONReduced expression of HLA class-I was an unfavorable prognostic factor in patients with positive expression of CT antigen, and represents an important hurdle to antigen-based cancer immunotherapy.