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 +淋巴瘤和急性淋巴母细胞性白血病。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，为了使CAR达到当前的结果，必须对CAR结构进行几处修改。CAR-T策略仍然有很大的改进空间，以提高临床疗效并克服某些仍会影响广泛应用的局限性。一个主要问题是功能障碍性获得性表型，由肿瘤抑制分子引起，甚至由CAR分子本身加剧。在这方面，许多研究小组集中于常规结构的每个CAR分子结构域中的离散增量修饰，以寻求更好的响应。在这些重新设计策略中，包括结合亲和力的调节，共刺激分子配体的使用以及细胞内信号传导的控制。这篇综述的重点是涵盖CAR分子结构变化的最新报道，这些分子能够通过转导的细胞引发改善的反应。使用共刺激分子配体，并控制细胞内信号传导。这篇综述的重点是涵盖CAR分子结构变化的最新报道，这些分子能够通过转导的细胞引发改善的反应。使用共刺激分子配体，并控制细胞内信号转导。这篇综述的重点是涵盖CAR分子结构变化的最新报道，这些分子能够通过转导的细胞引发改善的反应。