Strategies for Improving CAR T Cell Persistence in Solid Tumors.

Simple Summary: CAR T cell therapies have been successful at treating patients with blood cancers and are now FDA-approved therapies for various types of leukemias and lymphomas. However, there are many challenges to using CAR T cells to treat patients with solid tumors. In fact, no CAR T cell product is currently FDA-approved in this context. Optimism remains for this promising therapy to treat solid tumors in the future. Many different strategies are being employed to improve the efficacy of next-generation T cell products. This review focuses specifically on one key problem with current CAR T cell products for solid tumors: persistence. We describe the emerging strategies being used to improve this element of CAR T cell therapy. 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. [ABSTRACT FROM AUTHOR]