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Better by design: What to expect from novel CAR-engineered cell therapies?

嵌合抗原受体 细胞疗法 免疫疗法 诱导多能干细胞 癌症免疫疗法 免疫系统 抗原 免疫学 外周血单个核细胞 癌症研究 医学 干细胞 生物 胚胎干细胞 细胞生物学 基因 生物化学 体外
作者
Vera Luginbuehl,Eytan Abraham,Karin Kovar,Richard Flaaten,A Müller
出处
期刊:Biotechnology Advances [Elsevier]
卷期号:58: 107917-107917 被引量:20
标识
DOI:10.1016/j.biotechadv.2022.107917
摘要

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 (αβ) T cells, other immune cells such as natural killer (NK) cells, gamma delta (γδ) 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.
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