Engineering next-generation chimeric antigen receptor-T cells: recent breakthroughs and remaining challenges in design and screening of novel chimeric antigen receptor variants
Year: 2024
Type: article
Abstract: Chimeric antigen receptor (CAR) T cells are a powerful treatment against hematologic cancers. The functional phenotype of a CAR-T cell is influenced by the domains that comprise the synthetic receptor. Typically, the potency of therapeutic CAR-T cell candidates is assessed by preclinical functional assays and mouse models (i.e. human tumor xenografts). However, to date, only a few sets of domains (e.g. CD8, CD28, 41BB) have been extensively tested in preclinical assays and human clinical studies. To characterize the efficiency of a CAR, different assays have been utilized to analyze T cell phenotypes, such as expansion, cytotoxicity, secretome, and persistence. However, each of these previous studies evaluated the importance of an assay differently, resulting in a wide range of functionally diverse CARs. In this review, we highlight recent (high-throughput) methods to analyze CAR domains and demonstrate their impact on inducing T cell phenotypes and activity. We also describe advances in computational methods and their potential for identifying CAR variants with enhanced properties. Finally, we reflect on the need for a standardized scoring system to support the clinical development of next-generation CARs.
Authors: Mei, Anna, Letscher, Kevin P., Reddy, Sai
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6928640305
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