第二代嵌合抗原受體(CARs)能夠重定位和重編程的T細胞，以增加他們的抗腫瘤功效。近期發表於《自然評論:藥物發現》(Nature reviews. Drug discovery)2015年6月的一篇文章對第二代嵌合抗原受體的藥理學進行了綜述。

作者指出聯合刺激和共同刺激區將這些嵌合抗原受體(CARs)合並，準確確定了工程化T細胞的功能，分化，代謝和持久性。靶向CD19的嵌合抗原受體(CARs)，能夠與CD28或4-1BB信號域結合，這是最新公開的研究成果，在難治型B細胞惡性腫瘤中表現出非常顯著的抑製率。最近的數據表明，基於CD28的嵌合抗原受體(CARs)介導增殖反應和提高效應子功能，而基於4-1BB的嵌合抗原受體(CARs)能夠誘導更多的T細胞積累，增加效力。這些不同的動力學特征表明，以嵌合抗原受體(CARs)為主的T細胞能夠用於治療各種癌症，將被進一步開發。免疫藥理學的新領域正在出現。

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.