第二代嵌合抗原受体(CARs)能够重定位和重编程的T细胞，以增加他们的抗肿瘤功效。近期发表于《自然评论:药物发现》(Nature reviews. Drug discovery)2015年6月的一篇文章对第二代嵌合抗原受体的药理学进行了综述。

        作者指出联合刺激和共同刺激区将这些嵌合抗原受体(CARs)合并，准确确定了工程化T细胞的功能，分化，代谢和持久性。靶向CD19的嵌合抗原受体(CARs)，能够与CD28或4-1BB信号域结合，这是最新公开的研究成果，在难治型B细胞恶性肿瘤中表现出非常显著的抑制率。最近的数据表明，基于CD28的嵌合抗原受体(CARs)介导增殖反应和提高效应子功能，而基于4-1BB的嵌合抗原受体(CARs)能够诱导更多的T细胞积累，增加效力。这些不同的动力学特征表明，以嵌合抗原受体(CARs)为主的T细胞能够用于治疗各种癌症，将被进一步开发。免疫药理学的新领域正在出现。

        原文摘要：

        The pharmacology of second-generation chimeric antigen receptors.

        van der Stegen SJ1, Hamieh M1, Sadelain M1.

        Author information

        Abstract

        Second-generation chimeric antigen receptors (CARs) retarget and reprogramme T cells to augment their antitumour efficacy. The combined activating and co-stimulatory domains incorporated in these CARs critically determine the function, differentiation, metabolism and persistence of engineered T cells. CD19-targeted CARs that incorporate CD28 or 4-1BB signalling domains are the best known to date. Both have shown remarkable complete remission rates in patients with refractory B cell malignancies. Recent data indicate that CD28-based CARs direct a brisk proliferative response and boost effector functions, whereas 4-1BB-based CARs induce a more progressive T cell accumulation that may compensate for less immediate potency. These distinct kinetic features can be exploited to further develop CAR-based T cell therapies for a variety of cancers. A new field of immunopharmacology is emerging.