肿瘤细胞治疗研究
英文原题：Better by design: What to expect from novel CAR-engineered cell therapies?
嵌合抗原受体（CAR）技术，尤其是CAR-T细胞，自证明对多种血液系统恶性肿瘤有效以来，已成为癌症免疫治疗中一种新的强大工具。
嵌合抗原受体（CAR）技术，尤其是CAR-T细胞，自其在多种血液系统恶性肿瘤中显示出疗效以来，已成为癌症免疫治疗中一种新的强大工具。然而，尽管CAR-T细胞治疗产品的临床结果令人鼓舞，但仍有相当比例的患者未能获得满意的缓解，或出现复发。此外，由于肿瘤微环境和缺乏特异性可靶向的肿瘤抗原，CAR-T细胞在实体瘤中的应用仍然受限。目前市场上所有产品以及大多数研究性CAR-T细胞疗法均为自体疗法，使用患者自身的外周血单个核细胞作为起始材料来生产患者特异性批次。因此，替代细胞来源正在研究中（例如来自至少部分人类白细胞抗原（HLA）匹配的健康供者的同种异体细胞、来自非HLA匹配供者的通用“第三方”细胞、脐血来源细胞、永生化细胞系或由诱导多能干细胞分化而来的细胞）。然而，CAR工程化细胞的基因修饰、用于扩增细胞的生物工艺以及改进的供应链仍然复杂且昂贵。为克服与CAR-T技术相关的缺陷，新的CAR设计已被用于对来源于αβ（）T细胞、其他免疫细胞如自然杀伤（NK）细胞、γδ（）T细胞、巨噬细胞或树突状细胞的细胞进行基因工程改造。本综述旨在激发关于超越CAR-T细胞的下一代CAR工程化细胞疗法的思路，从而为癌症的临床管理提供有效、安全且可负担的疗法。为实现这一目标，我们提供了一项多学科概述，涵盖了广泛的关键方面：CAR设计、开发与制造技术、药理学概念以及CAR工程化细胞疗法的临床应用。这些领域中的每一个都采用了大量突破性的科学进展，在其交界面上发生了协调而复杂的过程与产品开发。
Chimeric antigen receptor (CAR) technology, and CAR-T cells in particular, have emerged as a new and powerful tool in cancer immunotherapy since demonstrating efficacy against several hematological malignancies. However, despite encouraging clinical results of CAR-T cell therapy products, a significant proportion of patients do not achieve satisfactory responses, or relapse. In addition, CAR-T cell applications to solid tumors is still limited due to the tumor microenvironment and lack of specifically targetable tumor antigens. All current products on the market, as well as most investigational CAR-T cell therapies, are autologous, using the patient's own peripheral blood mononuclear cells as starting material to manufacture a patient-specific batch. Alternative cell sources are, therefore, under investigation (e.g. allogeneic cells from an at least partially human leukocyte antigen (HLA)-matched healthy donor, universal "third-party" cells from a non-HLA-matched donor, cord blood-derived cells, immortalized cell lines or cells differentiated from induced pluripotent stem cells). However, genetic modifications of CAR-engineered cells, bioprocesses used to expand cells, and improved supply chains are still complex and costly. To overcome drawbacks associated with CAR-T technologies, novel CAR designs have been used to genetically engineer cells derived from alpha beta ( ) T cells, other immune cells such as natural killer (NK) cells, gamma delta ( ) T cells, macrophages or dendritic cells. This review endeavours to trigger ideas on the next generation of CAR-engineered cell therapies beyond CAR-T cells and, thus, will enable effective, safe and affordable therapies for clinical management of cancer. To achieve this, we present a multidisciplinary overview, addressing a wide range of critical aspects: CAR design, development and manufacturing technologies, pharmacological concepts and clinical applications of CAR-engineered cell therapies. Each of these fields employs a large number of ground-breaking scientific advances, where coordinated and complex process and product development occur at their interfaces.
MEMBER ACCOUNT
登录成功会直接打开下一页。
