美国加州大学旧金山分校Wendell A. Lim小组实现T细胞识别程序的精细设计。相关论文发表在2020年11月27日出版的《科学》杂志上。
Title: Precise T cell recognition programs designed by transcriptionally linking multiple receptors
Author: 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
Issue&Volume: 2020/11/27
Abstract: 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.
DOI: 10.1126/science.abc6270
Source: https://science.sciencemag.org/content/370/6520/1099