{"title":"Allogeneic “Off-the-Shelf” CAR T cells: Challenges and advances","authors":"","doi":"10.1016/j.beha.2024.101566","DOIUrl":null,"url":null,"abstract":"<div><p>Chimeric antigen receptor (CAR) T cell therapy has shown impressive clinical efficacy in B cell malignancies and multiple myeloma, leading to the approval of six CAR T cell products by the U.S. Food and Drug Administration (FDA) to date. However, broad application of these autologous (patient-derived) CAR T cells is limited by several factors, including high production costs, inconsistent product quality, contamination of the cell product with malignant cells, manufacturing failure especially in heavily pre-treated patients, and lengthy manufacturing times resulting in subsequent treatment delay. A potential solution to these barriers lies in the use of allogeneic “off-the-shelf” CAR T cells produced from healthy donors. Many efforts are underway to make allogeneic CAR T cells a safe and efficacious therapeutic option. In this review, we will discuss the major challenges that have to be addressed to successfully develop allogeneic CAR T cell therapies, specifically graft-versus-host disease (GVHD) and host-mediated immune rejection of the donor cells. Furthermore, we will summarize approaches that have been utilized to overcome these limitations, focusing on the use of gene editing technologies and strategies employing alternative cell populations as the source for allogeneic CAR T cell production.</p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Best Practice & Research Clinical Haematology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S152169262400032X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Chimeric antigen receptor (CAR) T cell therapy has shown impressive clinical efficacy in B cell malignancies and multiple myeloma, leading to the approval of six CAR T cell products by the U.S. Food and Drug Administration (FDA) to date. However, broad application of these autologous (patient-derived) CAR T cells is limited by several factors, including high production costs, inconsistent product quality, contamination of the cell product with malignant cells, manufacturing failure especially in heavily pre-treated patients, and lengthy manufacturing times resulting in subsequent treatment delay. A potential solution to these barriers lies in the use of allogeneic “off-the-shelf” CAR T cells produced from healthy donors. Many efforts are underway to make allogeneic CAR T cells a safe and efficacious therapeutic option. In this review, we will discuss the major challenges that have to be addressed to successfully develop allogeneic CAR T cell therapies, specifically graft-versus-host disease (GVHD) and host-mediated immune rejection of the donor cells. Furthermore, we will summarize approaches that have been utilized to overcome these limitations, focusing on the use of gene editing technologies and strategies employing alternative cell populations as the source for allogeneic CAR T cell production.
嵌合抗原受体(CAR)T 细胞疗法在 B 细胞恶性肿瘤和多发性骨髓瘤的临床疗效令人印象深刻,美国食品药品管理局(FDA)迄今已批准了六种 CAR T 细胞产品。然而,这些自体(源自患者)CAR T 细胞的广泛应用受到几个因素的限制,包括生产成本高、产品质量不稳定、细胞产品受到恶性细胞污染、生产失败(尤其是在预处理严重的患者中)以及生产时间过长导致后续治疗延迟。解决这些障碍的潜在办法是使用从健康供体中提取的异体 "现成 "CAR T 细胞。为了使异体 CAR T 细胞成为一种安全有效的治疗选择,我们正在做出许多努力。在这篇综述中,我们将讨论成功开发异体 CAR T 细胞疗法必须应对的主要挑战,特别是移植物抗宿主疾病(GVHD)和宿主介导的供体细胞免疫排斥反应。此外,我们还将总结克服这些局限性的方法,重点是基因编辑技术的使用和采用替代细胞群作为异体 CAR T 细胞生产来源的策略。
期刊介绍:
Best Practice & Research Clinical Haematology publishes review articles integrating the results from the latest original research articles into practical, evidence-based review articles. These articles seek to address the key clinical issues of diagnosis, treatment and patient management. Each issue follows a problem-orientated approach which focuses on the key questions to be addressed, clearly defining what is known and not known, covering the spectrum of clinical and laboratory haematological practice and research. Although most reviews are invited, the Editor welcomes suggestions from potential authors.