免疫原性
嵌合抗原受体
医学
免疫系统
临床试验
CD19
免疫疗法
免疫学
汽车T细胞治疗
细胞疗法
抗原
癌症
细胞
内科学
生物
遗传学
作者
Dimitrios L. Wagner,Enrico Fritsche,Michael A. Pulsipher,Nabil Ahmed,Mohamad Hamieh,Meenakshi Hegde,Marco Ruella,Barbara Savoldo,Nirali N. Shah,Cameron J. Turtle,Alan S. Wayne,Mohamed Abou‐El‐Enein
标识
DOI:10.1038/s41571-021-00476-2
摘要
Patient-derived T cells genetically reprogrammed to express CD19-specific chimeric antigen receptors (CARs) have shown remarkable clinical responses and are commercially available for the treatment of patients with certain advanced-stage B cell malignancies. Nonetheless, several trials have revealed pre-existing and/or treatment-induced immune responses to the mouse-derived single-chain variable fragments included in these constructs. These responses might have contributed to both treatment failure and the limited success of redosing strategies observed in some patients. Data from early phase clinical trials suggest that CAR T cells are also associated with immunogenicity-related events in patients with solid tumours. Generally, the clinical implications of anti-CAR immune responses are poorly understood and highly variable between different CAR constructs and malignancies. These observations highlight an urgent need to uncover the mechanisms of immunogenicity in patients receiving CAR T cells and develop validated assays to enable clinical detection. In this Review, we describe the current clinical evidence of anti-CAR immune responses and discuss how new CAR T cell technologies might impact the risk of immunogenicity. We then suggest ways to reduce the risks of anti-CAR immune responses to CAR T cell products that are advancing towards the clinic. Finally, we summarize measures that investigators could consider in order to systematically monitor and better comprehend the possible effects of immunogenicity during trials involving CAR T cells as well as in routine clinical practice.
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