Ziva Moravec, Yue Zhao, Rhianne Voogd, Danielle R Cook, Seon Kinrot, Benjamin Capra, Haiyan Yang, Brenda Raud, Jiayu Ou, Jiekun Xuan, Teng Wei, Lili Ren, Dandan Hu, Jun Wang, John B A G Haanen, Ton N Schumacher, Xi Chen, Ely Porter, Wouter Scheper
T cell receptor (TCR) gene therapy is a potent form of cellular immunotherapy in which patient T cells are genetically engineered to express TCRs with defined tumor reactivity. However, the isolation of therapeutic TCRs is complicated by both the general scarcity of tumor-specific T cells among patient T cell repertoires and the patient-specific nature of T cell epitopes expressed on tumors. Here we describe a high-throughput, personalized TCR discovery pipeline that enables the assembly of complex synthetic TCR libraries in a one-pot reaction, followed by pooled expression in reporter T cells and functional genetic screening against patient-derived tumor or antigen-presenting cells...
April 23, 2024: Nature Biotechnology