T细胞受体
贪婪
过继性细胞移植
T细胞
受体
生物
细胞疗法
免疫学
嵌合抗原受体
免疫疗法
遗传增强
抗原
癌症研究
细胞
细胞生物学
免疫系统
基因
遗传学
作者
Elisa Kieback,Wolfgang Uckert
标识
DOI:10.1517/14712591003689998
摘要
Importance of the field: Adoptive therapy with T cell receptor- (TCR-) redirected T cells has shown efficacy in mouse tumor models and first responses in cancer patients. One prerequisite to elicit effective anti-tumor reactivity is the transfer of high-avidity T cells. Their generation, however, faces several technical difficulties. Target antigens are often expressed at low levels and their recognition requires the use of high-affine receptors. Yet, mainly low-affine TCRs have been isolated from tumor-infiltrating lymphocytes. Furthermore, upon transfer into a T cell the introduced receptor has to compete with the endogenous TCR.Areas covered in this review: This review discusses how the functional avidity of TCR-modified T cells can be enhanced by i) increasing the amount of introduced TCR heterodimers on the cell surface; and ii) generating receptors with high affinity. Risks of TCR gene therapy and possible safety mechanisms are discussed.What the reader will gain: The reader will gain an overview of the technical developments in TCR and T cell engineering.Take home message: Despite technical obstacles, many advances have been made in the generation of high-avidity T cells expressing enhanced TCRs. Mouse studies and clinical trials will evaluate the effect of these improvements.
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