嵌合抗原受体修饰细胞治疗的现状及调控研究

技术资料下载地址: http://www.ncbi.nlm.nih.gov/pubmed/26895243
文献来源: Arch Pharm Res

Current status and regulatory perspective of chimeric antigen receptor-modified T cell therapeutics.
Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a new modality for cancer immunotherapy due to their potent efficacy against terminal cancers. CAR-Ts are reported to exert higher efficacy than monoclonal antibodies and antibody-drug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors. CAR-Ts are classified as first-, second- and third-generation, depending on the intracellular signaling domain number of T cell receptors. This review covers the current status of CAR-T research, including basic proof-of-concept investigations at the cell and animal levels. Currently ongoing clinical trials of CAR-T worldwide are additionally discussed. Owing to the lack of existing approved products, several unresolved concerns remain with regard to safety, efficacy and manufacturing of CAR-T, as well as quality control issues. In particular, the cytokine release syndrome is the major side-effect impeding the successful development of CAR-T in clinical trials. Here, we have addressed the challenges and regulatory perspectives of CAR-T therapy.

嵌合抗原受体修饰细胞治疗的现状及调控研究

嵌合抗原受体修饰T细胞（CAR-T）由于其对抗晚期癌症强大的疗效,。已经成为一种新的形式的癌症免疫疗法。据报道，CAR-T比单克隆抗体和抗体-药物结合物具有更高的疗效，其通过与T细胞受体加工的T细胞具有不同的作用机制。通过转导基因编码癌症抗原识别信号链的Fv片段，将其融合T细胞受体细胞内信号域蛋白，从而构建这样的CAR-T细胞。根据T细胞受体内的信号域数量，被分为一代、二代和三代CAR-T。这篇综述包含了目前CAR-T研究的一些情况，包含在细胞和动物水平上的基础研究。此外，还讨论了目前在全球范围内正在进行的CAR-T临床试验。由于存在一些没有解决的问题，如安全性、有效性、CAR-T的制造以及质量控制方面，到目前为止仍然没有批准通过的产品。尤其是，细胞因子风暴仍然是影响CAR-T临床试验成功的主要副作用。因此，我们在文章中解决这方面的挑战和CAR-T治疗中的调节研究。

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