The antitumor activity of the human FOLR1-specific monoclonal antibody, farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent cellular cytotoxicity
The antitumor activity of the human FOLR1-specific monoclonal antibody, farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent cellular cytotoxicity
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DOI：
10.4161/cbt.26106
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发表时间：
2013-01-01
影响因子：
3.6
通讯作者：
Grasso, Luigi
中科院分区：
文献类型：
--
作者：
Lin, JianMin;Spidel, Jared L.;Grasso, Luigi
由于其高死亡率，卵巢癌是妇女死亡的主要原因，也是一个高度未满足的医疗需求。需要有效且耐受性良好的新治疗剂，并且具有直接药理学作用或可刺激免疫应答的癌症抗原特异性单克隆抗体代表了用于治疗这种疾病的一类有希望的药剂。人叶酸受体α（FOLR 1）在卵巢癌中过表达，但在正常组织中基本上不存在，似乎在卵巢癌的转化表型、顺铂敏感性和叶酸耗尽条件下的生长中发挥作用，因此具有作为被动免疫治疗靶点的潜力。抗FOLR 1单克隆抗体MORAb-003（法来珠单抗）先前显示可引发抗体依赖性细胞毒性（ADCC）并抑制裸鼠中人肿瘤异种移植物的肿瘤生长。由于其有前途的临床前概况，farletuzumab已在临床试验中被评估为卵巢癌的潜在治疗剂。在这份报告中，我们证明了farletuzumab对卵巢癌实验模型的抗肿瘤作用是由其ADCC活性介导的。
Because of its high mortality rate, ovarian cancer is a leading cause of death among women and a highly unmet medical need. New therapeutic agents that are effective and well tolerated are needed and cancer antigen-specific monoclonal antibodies that have direct pharmacologic effects or can stimulate immunological responses represent a promising class of agents for the treatment of this disease. The human folate receptor alpha (FOLR1), which is overexpressed in ovarian cancer but largely absent in normal tissues, appears to play a role in the transformed phenotype in ovarian cancer, cisplatin sensitivity, and growth in depleted folate conditions and therefore has potential as a target for passive immunotherapy. The anti-FOLR1 monoclonal antibody MORAb-003 (farletuzumab) was previously shown to elicit antibody dependent cellular cytotoxicity (ADCC) and inhibit tumor growth of human tumor xenografts in nude mice. Because of its promising preclinical profile, farletuzumab has been evaluated in clinical trials as a potential therapeutic agent for ovarian cancer. In this report, we demonstrated that farletuzumab's antitumor effect against an experimental model of ovarian cancer is mediated by its ADCC activity.