Development of novel biomarker for cetuximab therapy in lung cancer

开发西妥昔单抗治疗肺癌的新型生物标志物

• 批准号: 21590994
• 负责人: CHIKUMI Hiroki
• 金额: $ 2.91万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590994/
• 关键词: 肺癌; 薬剤反応性; 内科; 薬剤反応

An anti-EGFR monoclonal antibody, cetuximab, has been developed as a novel molecular targeting therapy in lung cancer. In this study, we developed a novel biomarker for cetuximab to select the subset of patients who will show a meaningful clinical response, by using our original finding that the main anti-cancer mechanism of cetuximab is immunological antitumor activity such as antibody-dependent cellular cytotoxicity(ADCC). As a result, we revealed that ULBP2 is the most significant NKG2D ligands, which are known as the activating ligands of NK cells, and that soluble form of ULBP2(sULBP2) directly suppresses both the cytolytic activity and cetuximab induced ADCC activity of host NK cells. Therefore, administration of cetuximab to the patients with low levels of sULBP, or the patients after surgery or chemotherapy with lowest sULBP2 levels is the best strategy for cetuximab treatment for lung cancer.

抗 EGFR 单克隆抗体西妥昔单抗已被开发为肺癌的新型分子靶向疗法。在这项研究中，我们开发了一种新的西妥昔单抗生物标志物，利用我们最初的发现，即西妥昔单抗的主要抗癌机制是抗体依赖性细胞毒性（ADCC）等免疫抗肿瘤活性，来选择将表现出有意义的临床反应的患者子集。结果，我们发现ULBP2是最重要的NKG2D配体，被称为NK细胞的激活配体，并且可溶形式的ULBP2（sULBP2）直接抑制宿主NK细胞的细胞溶解活性和西妥昔单抗诱导的ADCC活性。因此，对sULBP水平较低的患者或手术或化疗后sULBP2水平最低的患者给予西妥昔单抗是西妥昔单抗治疗肺癌的最佳策略。

项目成果

Soluble UL16 binding protein 2 is elevated in the sera of lung cancer patients

肺癌患者血清中可溶性 UL16 结合蛋白 2 升高

• 发表时间: 2010
• 作者: Yamaguchi K;Chikumi H;Kinoshita N;Shimizu A;Hashimoto K;Kurai J;Yamasaki A;Nakamoto M;Matsumoto S;Takata M;Igishi T;Burioka N;Shimizu E
• 通讯作者: Shimizu E

Antibody-dependent cellular cytotoxicity mediated by cetuximab against mesothelioma cells

西妥昔单抗介导的抗体依赖性细胞毒性对间皮瘤细胞

• 发表时间: 2010
• 作者: Chikumi H;Kurai J;Kinoshita N;Nakamoto M;Matsumoto S;Igishi T;Hamada H;Yano S;Shimizu E
• 通讯作者: Shimizu E

Lack of AKT activation in lung cancer cells with EGFR mutation is a novel marker of cetuximab sensitivity

• DOI: 10.4161/cbt.19238
• 发表时间: 2012-04-01
• 期刊: CANCER BIOLOGY & THERAPY
• 影响因子: 3.6
• 作者: Takata, Miyako;Chikumi, Hiroki;Shimizu, Eiji
• 通讯作者: Shimizu, Eiji

Circulating serum ULBP2 in patients with various lung diseases

各种肺部疾病患者循环血清ULBP2

• 发表时间: 2012
• 作者: Kinoshita N;Chikumi H;Yamaguchi K;Takata M;Nakamoto M;Kodani M;Matsumoto S;Kawasaki Y;Tadashi I;Shimizu E
• 通讯作者: Shimizu E

Development of a novel combination therapy using cetuximab

使用西妥昔单抗开发新型联合疗法

• 发表时间: 2012
• 作者: Takata M;Shimizu E;et al
• 通讯作者: et al