CAR-T细胞临床药理学：连接细胞药理学到药代动力学和抗肿...

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Clinical pharmacology of CAR-T cells: Linking cellular pharmacodynamics to pharmacokinetics and antitumor effects.

Adoptive cell transfer of T cells genetically modified with tumor-reactive chimeric antigen receptors (CARs) is a rapidly emerging field in oncology, which in preliminary clinical trials has already shown striking antitumor efficacy. Despite these premises, there are still a number of open issues related to CAR-T cells, spanning from their exact mechanism of action (pharmacodynamics), to the factors associated with their in vivo persistence (pharmacokinetics), and, finally, to the relative contribution of each of the two in determining the antitumor effects and accompanying toxicities. In light of the unprecedented curative potential of CAR-T cells and of their predicted wide availability in the next few years, in this review we will summarize the current knowledge on the clinical pharmacology aspects of what is anticipated to be a brand new class of biopharmaceuticals to join the therapeutic armamentarium of cancer doctors.

KEYWORDS:

Adoptive cell transfer; Cancer immunotherapy; Clinical results; Genetically modified T cells; Pharmacokinetics/pharmacodynamics; Toxicities

CAR-T细胞临床药理学：连接细胞药理学到药代动力学和抗肿瘤效益

具有肿瘤细胞反应性的嵌合抗原受体（CARs）修饰的过继T细胞移植是一个肿瘤学新兴的领域，在初步的临床试验中已经显示出惊人的抗肿瘤疗效。尽管有这些前提，仍然有一批与 CAR-T细胞有关的开放问题，从其确切的作用机制（药效学），与他们在体内持久性（药代动力学）的相关因素，最后，根据两者确定其抗肿瘤作用和毒副作用。按照其前所未有的潜在疗效和其在接下来几年内可用性的预测，在这篇综述中，我们总结了目前与CARs相关的临床药理学的一些知识。

关键词：

细胞移植；肿瘤免疫治疗；临床结果；基因修饰细胞；药代动力学/药效学；毒性