Wittling Megen C, Cole Anna C, Brammer Brianna, Diatikar Kailey G, Schmitt Nicole C, Paulos Chrystal M
Department of Surgery/Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Cancers (Basel). 2024 Aug 16;16(16):2858. doi: 10.3390/cancers16162858.
CAR T cells require optimization to be effective in patients with solid tumors. There are many barriers affecting their ability to succeed. One barrier is persistence, as to achieve an optimal antitumor response, infused CAR T cells must engraft and persist. This singular variable is impacted by a multitude of factors-the CAR T cell design, lymphodepletion regimen used, expansion method to generate the T cell product, and more. Additionally, external agents can be utilized to augment CAR T cells, such as the addition of novel cytokines, pharmaceutical drugs that bolster memory formation, or other agents during either the ex vivo expansion process or after CAR T cell infusion to support them in the oppressive tumor microenvironment. This review highlights many strategies being used to optimize T cell persistence as well as future directions for improving the persistence of infused cells.
嵌合抗原受体(CAR)T细胞需要优化才能对实体瘤患者有效。存在许多影响其成功的障碍。一个障碍是持久性,因为要实现最佳的抗肿瘤反应,注入的CAR T细胞必须植入并持续存在。这个单一变量受到多种因素的影响——CAR T细胞设计、所使用的淋巴细胞清除方案、产生T细胞产品的扩增方法等等。此外,可以利用外部因子来增强CAR T细胞,例如在体外扩增过程中或CAR T细胞注入后添加新型细胞因子、促进记忆形成的药物或其他因子,以在压迫性肿瘤微环境中支持它们。本综述强调了许多用于优化T细胞持久性的策略以及改善注入细胞持久性的未来方向。