Allogeneic mesenchymal stromal cells (MSCs) are a safe treatment option for many disorders of the immune system. However, clinical trials using MSCs have shown inconsistent therapeutic efficacy, mostly owing to MSCs providing insufficient immunosuppression in target tissues. Here we show that antigen-specific immunosuppression can be enhanced by genetically modifying MSCs with chimaeric antigen receptors (CARs), as we show for E-cadherin-targeted CAR-MSCs for the treatment of graft-versus-host disease in mice. CAR-MSCs led to superior T-cell suppression and localization to E-cadherin⁺ colonic cells, ameliorating the animals’ symptoms and survival rates. On antigen-specific stimulation, CAR-MSCs upregulated the expression of immunosuppressive genes and receptors for T-cell inhibition as well as the production of immunosuppressive cytokines while maintaining their stem cell phenotype and safety profile in the animal models. CAR-MSCs may represent a widely applicable therapeutic technology for enhancing immunosuppression.

同种异体间充质基质细胞（MSC）是许多免疫系统疾病的安全治疗选择。然而，使用间充质干细胞的临床试验显示治疗效果不一致，这主要是由于间充质干细胞在靶组织中提供的免疫抑制不足。在这里，我们表明，可以通过用嵌合抗原受体（CAR）对 MSC 进行基因修饰来增强抗原特异性免疫抑制，正如我们展示的 E-钙粘蛋白靶向 CAR-MSC 用于治疗小鼠移植物抗宿主病一样。 CAR-MSC 导致对 T 细胞的卓越抑制和定位到 E-钙粘蛋白⁺结肠细胞，从而改善动物的症状和存活率。在抗原特异性刺激下，CAR-MSC 上调免疫抑制基因和 T 细胞抑制受体的表达以及免疫抑制细胞因子的产生，同时保持其在动物模型中的干细胞表型和安全性。 CAR-MSCs可能代表了一种广泛应用的增强免疫抑制的治疗技术。