Though TCRs have been subject to limited engineering in the context of therapeutic design and optimization, they are used largely as found in nature. On the other hand, CARs are artificial, composed of different segments of proteins that function in the immune system. This characteristic raises the possibility of altered response to immune regulatory stimuli. Here we describe a large-scale, systematic comparison of CARs and TCRs across 5 different pMHC targets, with a total of 19 constructs examined in vitro. These functional measurements include CAR- and TCR-mediated activation, proliferation, and cytotoxicity in both acute and chronic settings. Surprisingly, we find no consistent difference between CARs and TCRs as receptor classes with respect to their relative sensitivity to major regulators of T cell activation: PD-L1, CD80/86 and IL-2. Though TCRs often emerge from human blood directly as potent, selective receptors, CARs must be heavily optimized to attain these properties for pMHC targets. Nonetheless, when iteratively improved and compared head to head in functional tests, CARs appear remarkably similar to TCRs with respect to immune modulation.

尽管 TCR 在治疗设计和优化的背景下受到了有限的工程设计，但它们主要在自然界中使用。另一方面，CARs 是人造的，由在免疫系统中起作用的不同蛋白质片段组成。这种特征增加了对免疫调节刺激的反应改变的可能性。在这里，我们描述了对 5 个不同 pMHC 靶标的 CAR 和 TCR 的大规模系统比较，总共对 19 种构建体进行了体外检查. 这些功能测量包括急性和慢性环境中 CAR 和 TCR 介导的激活、增殖和细胞毒性。令人惊讶的是，我们发现作为受体类别的 CAR 和 TCR 在它们对 T 细胞活化的主要调节因子 PD-L1、CD80/86 和 IL-2 的相对敏感性方面没有一致的差异。尽管 TCR 通常直接从人类血液中作为有效的选择性受体出现，但必须对 CAR 进行大量优化才能获得 pMHC 靶标的这些特性。尽管如此，当在功能测试中反复改进并进行正面比较时，CAR 在免疫调节方面似乎与 TCR 非常相似。