来源：源正细胞

第二代CARs嵌合抗原受体重定向编程T细胞能有效增强其抗肿瘤效应。CAR-T技术中设计的激活及共刺激结构区决定了编辑后的T细胞功能、分化、代谢以及能否持续工作的能力。

目前为止，已知最好的激活与共刺激结构区为CD-19CARs受体整合CD28或4-1BB信号区。基于CD28或4-1BB信号区改造的CAR-T细胞，二者都能够针对难治性B淋巴瘤显示出显著的完全缓解率。

近期的研究数据显示基于CD28信号区嵌合受体能够敏锐的刺激出增殖反应并且提高效应因子的功能，而基于4-1BB信号区嵌合受体能够进一步诱导T细胞的增殖和富集。这些显著的动力学特征能够为进一步开发基于CAR-T技术的肿瘤免疫细胞治疗提供新的途径和方法，有望于解决其他种类的肿瘤。

原文标题：

The pharmacology of second-generation chimeric antigen receptors

摘要：

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.

2015-07-22