Programmed death-1: therapeutic success after more than 100 years of cancer immunotherapy.
Programmed death-1: therapeutic success after more than 100 years of cancer immunotherapy.
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DOI：
10.1002/anie.201307906
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发表时间：
2014-02-24
影响因子：
16.6
通讯作者：
Holak, Tad A.
中科院分区：
文献类型：
--
作者：
Doemling, Alexander;Holak, Tad A.
120多年前，威廉·科利首次测试了通过使用细菌制品治疗实体瘤患者来操纵免疫系统抗癌的概念。[1]重复性和有效性低，副作用严重，导致临床接受度低。20世纪初，现代免疫学之父保罗·埃尔利希提出了使用抗体来治疗靶向疾病的概念，现在通常被称为“神奇子弹”。[2]他提出免疫系统可能控制癌症。1975年塞萨尔·米尔斯坦和乔治·J·F·Kçhler引入杂交瘤技术以生产单抗，这导致了多种抗体用于抗癌的临床引入。[3]真正的免疫刺激方法包括具有里程碑意义的干扰素-α试验和后来的高剂量白介素2(IL-2)试验，以及在多种肿瘤类型的患者中使用所谓的淋巴因子激活的杀伤细胞。[4，5]虽然抗癌抗体在临床上已经很好地建立了，利用患者的免疫系统来排斥癌症--通常称为癌症免疫疗法--作为一种通过唤醒患者自身的免疫系统来实现持续临床成功的手段而苦苦挣扎(图1)。然而，最近针对程序性死亡受体(PD)的蛋白质-蛋白质相互作用的抗体的临床试验前景看好，这给人们带来了严重的希望，它们被认为是癌症治疗领域的“游戏规则改变者”。针对程序性死亡-1受体(PD-1)及其配体(PD-1L)的免疫检查点药物现已被选为2013年年度药物。
More than 120 years ago William Coley first tested the concept of manipulating the immune system to fight cancer by using bacterial products to treat patients with solid tumors.[1] Low reproducibility and efficacy and serious side effects led to a low acceptance in the clinic. At the beginning of the 20th century Paul Ehrlich, the father of modern immunology, introduced the concept of the use of antibodies to target diseases, nowadays often referred to as the “Magic Bullet”.[2] He proposed that the immune system might control cancer. The introduction of the hybridoma technology for the production of monoclonal antibodies by César Milstein and Georges JF Kçhler in 1975 has led to the clinical introduction of multiple antibodies to fight cancer.[3] Truly immune-stimulating approaches included the landmark trials of interferon-α and later high doses of interleukin-2 (IL-2) as well as socalled lymphokine-activated killer cells in patients with multiple tumor types.[4, 5] Although antibodies to fight cancer are well-established in the clinic, the use of the patient’s immune system to reject cancer—commonly called cancer immunotherapy—struggled as a means of achieving sustained clinical success by awakening the patient’s own immune system (Figure 1). Recent promising clinical trials of antibodies that target the protein–protein interactions of the receptor for programed death (PD), however, give cause for serious hope and they are considered to be a “game changer” in the area of cancer treatment. The immuno checkpoint drugs that target the programmed death-1 receptor (PD-1) and its ligand (PD-1L) have now been selected as the drug of the year for 2013.[6]
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影响因子：
10.3
作者：
ROSENBERG, SA;LOTZE, MT;STEINBERG, SM
通讯作者：
STEINBERG, SM
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
8.4
作者：
Robert, Caroline;Soria, Jean-Charles;Eggermont, Alexander M. M.
通讯作者：
Eggermont, Alexander M. M.
DOI：
10.1056/nejmoa1305133
发表时间：
2013-07-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hamid O;Robert C;Daud A;Hodi FS;Hwu WJ;Kefford R;Wolchok JD;Hersey P;Joseph RW;Weber JS;Dronca R;Gangadhar TC;Patnaik A;Zarour H;Joshua AM;Gergich K;Elassaiss-Schaap J;Algazi A;Mateus C;Boasberg P;Tumeh PC;Chmielowski B;Ebbinghaus SW;Li XN;Kang SP;Ribas A
通讯作者：
Ribas A
影响因子：
4
作者：
Milstein, C
通讯作者：
Milstein, C