Precise T cell recognition programs designed by transcriptionally linking multiple receptors

doi:10.1126/science.abc6270

GSTDTAP > 气候变化

DOI	10.1126/science.abc6270
	Precise T cell recognition programs designed by transcriptionally linking multiple receptors
	Jasper Z. Williams; Greg M. Allen; Devan Shah; Igal S. Sterin; Ki H. Kim; Vivian P. Garcia; Gavin E. Shavey; Wei Yu; Cristina Puig-Saus; Jennifer Tsoi; Antoni Ribas; Kole T. Roybal; Wendell A. Lim
	2020-11-27
发表期刊	Science
出版年	2020
英文摘要	There has been exciting progress in the field of cancer immunotherapy, which harnesses a patient's own immune system to kill cancer cells. However, achieving precise recognition of cancer cells remains challenging. Cells engineered with synthetic Notch (synNotch) receptors bind to specific antigens, and binding induces the expression of defined genes. Williams et al. used synNotch modules as transcriptional connectors that daisy-chain together multiple receptors. They engineered T cells that can recognize up to three target antigens expressed on or inside cancer cells and integrated these inputs to achieve NOT, AND, and OR logic. The engineered cells achieved precise recognition of targeted cancer cells. Science , this issue p. [1099][1] Living cells often identify their correct partner or target cells by integrating information from multiple receptors, achieving levels of recognition that are difficult to obtain with individual molecular interactions. In this study, we engineered a diverse library of multireceptor cell-cell recognition circuits by using synthetic Notch receptors to transcriptionally interconnect multiple molecular recognition events. These synthetic circuits allow engineered T cells to integrate extra- and intracellular antigen recognition, are robust to heterogeneity, and achieve precise recognition by integrating up to three different antigens with positive or negative logic. A three-antigen AND gate composed of three sequentially linked receptors shows selectivity in vivo, clearing three-antigen tumors while ignoring related two-antigen tumors. Daisy-chaining multiple molecular recognition events together in synthetic circuits provides a powerful way to engineer cellular-level recognition. [1]: /lookup/doi/10.1126/science.abc6270
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/304886
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jasper Z. Williams,Greg M. Allen,Devan Shah,et al. Precise T cell recognition programs designed by transcriptionally linking multiple receptors[J]. Science,2020.
APA	Jasper Z. Williams.,Greg M. Allen.,Devan Shah.,Igal S. Sterin.,Ki H. Kim.,...&Wendell A. Lim.(2020).Precise T cell recognition programs designed by transcriptionally linking multiple receptors.Science.
MLA	Jasper Z. Williams,et al."Precise T cell recognition programs designed by transcriptionally linking multiple receptors".Science (2020).