{"title":"高通量嵌合抗原受体 T 细胞发现的挑战和未来展望。","authors":"Savannah E Butler , Margaret E Ackerman","doi":"10.1016/j.copbio.2024.103216","DOIUrl":null,"url":null,"abstract":"<div><div>Novel chimeric antigen receptor (CAR) T cell designs are being developed to overcome challenges with tumor recognition, trafficking, on-target but off-tumor binding, cytotoxicity, persistence, and immune suppression within the tumor microenvironment. Whereas traditional CAR engineering is an iterative, hypothesis-driven process in which novel designs are rationally constructed and tested for <em>in vivo</em> efficacy, drawing from the fields of small-molecule and protein-based therapeutic discovery, we consider how high-throughput, functional screening technologies are beginning to be applied for the development of promising CAR candidates. We review how the development of high-throughput screening methods has the potential to streamline the CAR discovery process, ultimately improving efficiency and clinical efficacy.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103216"},"PeriodicalIF":7.1000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Challenges and future perspectives for high-throughput chimeric antigen receptor T cell discovery\",\"authors\":\"Savannah E Butler , Margaret E Ackerman\",\"doi\":\"10.1016/j.copbio.2024.103216\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Novel chimeric antigen receptor (CAR) T cell designs are being developed to overcome challenges with tumor recognition, trafficking, on-target but off-tumor binding, cytotoxicity, persistence, and immune suppression within the tumor microenvironment. Whereas traditional CAR engineering is an iterative, hypothesis-driven process in which novel designs are rationally constructed and tested for <em>in vivo</em> efficacy, drawing from the fields of small-molecule and protein-based therapeutic discovery, we consider how high-throughput, functional screening technologies are beginning to be applied for the development of promising CAR candidates. We review how the development of high-throughput screening methods has the potential to streamline the CAR discovery process, ultimately improving efficiency and clinical efficacy.</div></div>\",\"PeriodicalId\":10833,\"journal\":{\"name\":\"Current opinion in biotechnology\",\"volume\":\"90 \",\"pages\":\"Article 103216\"},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2024-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current opinion in biotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0958166924001526\",\"RegionNum\":2,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current opinion in biotechnology","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0958166924001526","RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
摘要
目前正在开发新型嵌合抗原受体(CAR)T细胞设计,以克服肿瘤识别、贩运、靶上但非肿瘤结合、细胞毒性、持久性以及肿瘤微环境中的免疫抑制等难题。传统的 CAR 工程是一个迭代、假设驱动的过程,在这个过程中,新的设计被合理地构建并测试体内疗效,我们借鉴了基于小分子和蛋白质的治疗发现领域的经验,同时考虑了高通量功能筛选技术如何开始应用于开发有前景的 CAR 候选者。我们回顾了高通量筛选方法的开发是如何简化 CAR 发现过程,最终提高效率和临床疗效的。
Challenges and future perspectives for high-throughput chimeric antigen receptor T cell discovery
Novel chimeric antigen receptor (CAR) T cell designs are being developed to overcome challenges with tumor recognition, trafficking, on-target but off-tumor binding, cytotoxicity, persistence, and immune suppression within the tumor microenvironment. Whereas traditional CAR engineering is an iterative, hypothesis-driven process in which novel designs are rationally constructed and tested for in vivo efficacy, drawing from the fields of small-molecule and protein-based therapeutic discovery, we consider how high-throughput, functional screening technologies are beginning to be applied for the development of promising CAR candidates. We review how the development of high-throughput screening methods has the potential to streamline the CAR discovery process, ultimately improving efficiency and clinical efficacy.
期刊介绍:
Current Opinion in Biotechnology (COBIOT) is renowned for publishing authoritative, comprehensive, and systematic reviews. By offering clear and readable syntheses of current advances in biotechnology, COBIOT assists specialists in staying updated on the latest developments in the field. Expert authors annotate the most noteworthy papers from the vast array of information available today, providing readers with valuable insights and saving them time.
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