Science gone translational: the OX40 agonist story.
Science gone translational: the OX40 agonist story.
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DOI：
10.1111/j.1600-065x.2011.01069.x
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发表时间：
2011-11
影响因子：
8.7
通讯作者：
Curti BD
中科院分区：
文献类型：
--
作者：
Weinberg AD;Morris NP;Kovacsovics-Bankowski M;Urba WJ;Curti BD
OX40 （CD134）是一种肿瘤坏死因子（TNF）受体，主要在活化的CD4+和CD8+ T细胞上表达，并在参与时传递有效的共刺激信号。OX40在T细胞受体参与后短暂表达，并在炎性病变（例如自身免疫破坏部位和肿瘤浸润淋巴细胞）内最新抗原活化的T细胞上上调。因此，它是一个有吸引力的目标来调节免疫反应：OX40阻断剂抑制不良炎症或OX40激动剂增强免疫反应。在本综述中，OX40激动剂增强抗肿瘤免疫，从而在小鼠肿瘤模型中产生治疗效果。普罗维登斯癌症中心的一个实验室和临床科学家团队合作，将癌症模型的临床前观察从实验室带到床边。这篇综述描述了从体外实验到临床前小鼠模型，再到首个OX40激动剂成功转化为临床治疗癌症患者的历程。
OX40 (CD134) is a tumor necrosis factor (TNF) receptor expressed primarily on activated CD4+ and CD8+ T cells and transmits a potent costimulatory signal when engaged. OX40 is transiently expressed after T-cell receptor engagement and is upregulated on the most recently antigen-activated T cells within inflammatory lesions (e.g. sites of autoimmune destruction and on tumor-infiltrating lymphocytes). Hence, it is an attractive target to modulate immune responses: OX40 blocking agents to inhibit undesirable inflammation or OX40 agonists to enhance immune responses. In regards to this review, OX40 agonists enhance anti-tumor immunity, which leads to therapeutic effects in mouse tumor models. A team of laboratory and clinical scientists at the Providence Cancer Center has collaborated to bring the preclinical observations in cancer models from the bench to the bedside. This review describes the journey from in vitro experiments through preclinical mouse models to the successful translation of the first OX40 agonist to the clinic for the treatment of patients with cancer.