The present application provides a method of producing a modified T cell with down-modulated endogenous T cell receptor (TCR). The present application also provides a method of producing a modified T cell with down-modulated endogenous TCR, further expressing a functional exogenous receptor, such as an engineered TCR (e.g., chimeric TCR), T cell antigen coupler (TAC), TAC-like chimeric receptor, or a chimeric antigen receptor (CAR). Further provided are modified T cells produced by the methods described herein, which may elicit reduced graft-versus-host disease (GvHD) response in a histoincompatible individual. Pharmaceutical compositions, kits, and methods of treatment are also provided.本申請案提供一種產生具有經下調內源T細胞受體(TCR)之經修飾T細胞之方法。本申請案亦提供一種產生具有經下調內源TCR之經修飾T細胞之方法，該經修飾T細胞進一步表現功能性外源受體，諸如經工程改造TCR(例如，嵌合TCR)、T細胞抗原偶合物(TAC)、TAC樣嵌合受體或嵌合抗原受體(CAR)。進一步提供藉由本文所述之方法產生的經修飾T細胞，其可在組織不相容性個體中引發降低之移植物抗宿主疾病(GvHD)反應。亦提供醫藥組合物、套組及治療方法。
