Methods and compositions for modulating CAR-T activity

Disclosed herein are engineered cells and/or low immunogenic cells, including engineered and/or low immunogenic stem cells, engineered and/or low immunogenic cells differentiated therefrom, engineered and/or low immunogenic CAR-T cells (primary or differentiated from engineered and/or low immunogenic stem cells), and related methods of using and generating the same. Provided herein are engineered and/or low immunogen cells that exhibit reduced expression of MHC class I and/or MHC class II human leukocyte antigens and T cell receptors. In some embodiments, such cells also exogenously express one or more tolerogenic factors, such as CD47 and one or more chimeric antigen receptors (CARs). 本文公开了工程化细胞和/或低免疫原性细胞，包括工程化和/或低免疫原性干细胞、从其分化的工程化和/或低免疫原性细胞、工程化和/或低免疫原性CAR-T细胞(原代或从工程化和/或低免疫原性干细胞分化)以及使用和生成它们的相关方法。本文提供了工程化和/或低免疫原性细胞，其表现出降低的MHC I类和/或MHC II类人白细胞抗原和T细胞受体的表达。在一些实施方案中，此类细胞还外源表达一种或多种致耐受因子，诸如CD47和一种或多种嵌合抗原受体(CAR)。