2025年6月24日出版的《细胞》杂志发表了中国科学家的一项最新研究成果。来自海军医科大学的徐沪济小组研究出iPSC衍生的CD19/BCMA CAR-NK治疗系统性硬化症。
本研究报道了iPSC衍生的CD19/BCMA双靶向嵌合抗原受体-自然杀伤（CAR-NK）细胞（QN-139b）在严重分化主题皮肤系统性硬化症患者中的首次人体应用。同种异体产物经过基因编辑，降低了同种异体反应性，提高了体内性能，未检测到结构性染色体异常。与CAR - T细胞治疗类似，该治疗导致显著的B细胞耗竭，毒性最小。在6个月的随访中，患者表现出明显的临床改善，包括自身抗体降低和纤维化逆转，这些对常规治疗具有耐药性。外周血的单细胞分析显示，治疗将B细胞转向更幼稚的表型，并消除了致病的B细胞。蛋白质组学研究表明，抑制炎症和纤维化，增强组织再生，改善血管生成。病理检查证实受累皮肤浸润淋巴细胞消失，皮肤和微血管结构恢复。这些发现表明，QN-139b是一种有希望的免疫调节治疗严重自身免疫性疾病。
附：英文原文
Title: An iPSC-derived CD19/BCMA CAR-NK therapy in a patient with systemic sclerosis
Author: Xiaobing Wang, Yi Zhang, Yi Jin, Lie Dai, Yanan Yue, Jiapan Hu, Xin Liu, Kun Pang, Songying Ye, Yue Chen, Wenjing Ye, Xiaofei Shi, Xin Ma, Lehang Guo, Yanfang Liu, Na Ta, Xiaofang Zhu, Li Lin, Jiazheng Wang, Ran Yan, Ping Wang, Xiaobin Song, Yixuan Zhou, Lina Zhou, Qing Wang, Tongxiang Guan, Ting Li, Ling Zhou, Weihua Pan, Yanran He, Xin Wu, Yingyong Xu, Luhan Yang, Huji Xu
Issue&Volume: 2025-06-24
Abstract: This study reports the first-in-human application of iPSC-derived CD19/BCMA dual-targeting chimeric antigen receptor-natural killer (CAR-NK) cells (QN-139b) in a patient with severe, diffuse cutaneous systemic sclerosis. The allogeneic product was genetically edited for reduced alloreactivity and improved in vivo performance, with no structural chromosomal abnormalities detected. The treatment led to significant B cell depletion with minimal toxicity, similar to CAR T cell therapy. The patient showed marked clinical improvements during the 6-month follow-up, including reduced autoantibodies and reversed fibrosis, which are resistant to conventional treatments. Single-cell analysis of peripheral blood revealed that the treatment shifted B cells toward more naive phenotypes and eliminated pathogenic B cells. Proteomic studies demonstrated suppression of inflammation and fibrosis, enhanced tissue regeneration, and improved angiogenesis. Pathological evaluation confirmed the elimination of infiltrated lymphocytes from affected skin along with restored skin and microvascular structure. These findings suggest QN-139b is a promising immune-modulatory treatment for severe autoimmune diseases.
DOI: 10.1016/j.cell.2025.05.038
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00625-7