Chimeric antigen receptor (CAR) T cell therapy consists of the gene transfer of a cassette encoding a receptor capable of redirecting the transduced T cell toward a specific cytotoxic response against tumor cells. The therapy has been providing a new perspective on some hematologic malignancies, such as CD19+ lymphomas and acute lympho-blastic leukemia. CAR-T cell-based therapies are now approved for commercial distribution in different countries. Over the years, several modifications were necessary in the CAR structure to get it to its current results. CAR-T strategies still have plenty of room for improvement in order to improve clinical benefits and to overcome some of the limitations that still impair broader application. One main issue is the dysfunctional acquired phenotype, provoked by tumor inhibitory molecules or even exacerbated signaling by the CAR molecule itself. In this regard, Many research groups focus on discrete incremental modifications in each of the CAR molecule domains of the conventional structure looking for better response. Among these redesign strategies are the modulation of the binding affinity, use of costimulatory molecule ligands, and control of intracellular signaling. This review focuses on the newest reports covering structure changes in the CAR molecule capable of eliciting improved responses by transduced cells.

中文翻译：

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嵌合抗原受体设计的结构决定因素。

嵌合抗原受体 (CAR) T 细胞疗法由编码受体的盒的基因转移组成，该受体能够将转导的 T 细胞重定向到针对肿瘤细胞的特定细胞毒性反应。该疗法为某些血液系统恶性肿瘤提供了新的视角，例如 CD19+ 淋巴瘤和急性淋巴细胞白血病。基于 CAR-T 细胞的疗法现已获准在不同国家进行商业销售。多年来，必须对 CAR 结构进行多次修改才能使其达到目前的结果。CAR-T 策略仍有很大的改进空间，以提高临床效益并克服一些仍然损害更广泛应用的局限性。一个主要问题是功能失调的获得性表型，由肿瘤抑制分子引起，甚至由 CAR 分子本身加剧信号传导。在这方面，许多研究小组专注于传统结构的每个 CAR 分子域中的离散增量修饰，以寻求更好的响应。这些重新设计的策略包括结合亲和力的调节、共刺激分子配体的使用和细胞内信号的控制。本综述侧重于最新报告，涵盖 CAR 分子中的结构变化，这些变化能够通过转导细胞引起改善的反应。共刺激分子配体的使用，以及细胞内信号的控制。本综述侧重于最新报告，涵盖 CAR 分子中的结构变化，这些变化能够通过转导细胞引起改善的反应。共刺激分子配体的使用，以及细胞内信号的控制。本综述侧重于最新报告，涵盖 CAR 分子中的结构变化，这些变化能够通过转导细胞引起改善的反应。