Zhang Shiyu, Zhou Min, Shao Chi, Zhao Yu, Liu Mingzhe, Ni Lei, Bao Zhiyao, Zhang Qiurui, Zhang Ting, Luo Qun, Qu Jieming, Xu Zuojun, Zuo Wei
Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Tongji Stem Cell Center, Tongji University, Shanghai, China.
Elife. 2025 Mar 4;13:RP102451. doi: 10.7554/eLife.102451.
In idiopathic pulmonary fibrosis (IPF) patients, alveolar architectures are lost and gas transfer function would decline, which cannot be rescued by conventional anti-fibrotic therapy. P63+ lung basal progenitor cells are reported to have potential to repair damaged lung epithelium in animal models, which need further investigation in clinical trials.
We cloned and expanded P63+ progenitor cells from IPF patients to manufacture cell product REGEND001, which were further characterized by morphology and single-cell transcriptomic analysis. Subsequently, an open-label, dose-escalation autologous progenitor cell transplantation clinical trial was conducted. We treated 12 patients with ascending doses of cells: 0.6x, 1x, 2x and 3.3x10 cells/kg bodyweight. The primary outcome was the incidence and severity of cell therapy-related adverse events (AEs); secondary outcome included other safety and efficacy evaluations.
P63+ basal progenitor cell was safe and tolerated at all doses, with no dose-limiting toxicity or cell therapy-related severe adverse events observed. Patients in three higher dose groups showed significant improvement of lung gas transfer function as well as exercise ability. Resolution of honeycomb lesion was observed in patients of higher dose groups.
REGEND001 has high safety profile and meanwhile encourages further efficacy exploration in IPF patients.
National High Level Hospital Clinical Research Funding (2022-PUMCH-B-108), National Key Research and Development Plan (2024YFA1108900, 2024YFA1108500), Jiangsu Province Science and Technology Special Project Funding (BE2023727), National Biopharmaceutical Technology Research Project Funding (NCTIB2023XB01011), Non-profit Central Research Institute Fund of Chinese Academy of Medical Science (2020-PT320-005), and Regend Therapeutics.
Chinese clinical trial registry: CTR20210349.
在特发性肺纤维化（IPF）患者中，肺泡结构遭到破坏，气体交换功能下降，传统抗纤维化治疗无法逆转这一情况。据报道，P63+肺基底祖细胞在动物模型中具有修复受损肺上皮的潜力，这需要在临床试验中进一步研究。
我们从IPF患者中克隆并扩增P63+祖细胞，制备细胞产品REGEND001，并通过形态学和单细胞转录组分析对其进行进一步表征。随后，开展了一项开放标签、剂量递增的自体祖细胞移植临床试验。我们用递增剂量的细胞治疗了12名患者：0.6x、1x、2x和3.3x10个细胞/千克体重。主要结局是细胞治疗相关不良事件（AE）的发生率和严重程度；次要结局包括其他安全性和有效性评估。
所有剂量的P63+基底祖细胞均安全且耐受性良好，未观察到剂量限制性毒性或细胞治疗相关的严重不良事件。三个高剂量组的患者肺气体交换功能以及运动能力均有显著改善。高剂量组患者的蜂窝状病变有所缓解。
REGEND001具有较高的安全性，同时也鼓励在IPF患者中进一步探索其疗效。
国家高水平医院临床研究资助（2022-PUMCH-B-108）、国家重点研发计划（2024YFA1108900, 2024YFA1108500）、江苏省科技专项资助（BE2023727）、国家生物制药技术研究项目资助（NCTIB2023XB01011）、中国医学科学院非营利性中央科研院所基金（2020-PT320-005）以及Regend Therapeutics。
中国临床试验注册中心：CTR20210349
