The therapeutic potential of donor-derived mesenchymal stromal cells (MSCs) has been investigated in diverse diseases¹, including steroid-resistant acute graft versus host disease (SR-aGvHD)². However, conventional manufacturing approaches are hampered by challenges with scalability and interdonor variability, and clinical trials have shown inconsistent outcomes^3,4. Induced pluripotent stem cells (iPSCs) have the potential to overcome these challenges, due to their capacity for multilineage differentiation and indefinite proliferation^5,6. Nonetheless, human clinical trials of iPSC-derived cells have not previously been completed. CYP-001 (iPSC-derived MSCs) is produced using an optimized, good manufacturing practice (GMP)-compliant manufacturing process. We conducted a phase 1, open-label clinical trial (no. NCT02923375) in subjects with SR-aGvHD. Sixteen subjects were screened and sequentially assigned to cohort A or cohort B (n = 8 per group). One subject in cohort B withdrew before receiving CYP-001 and was excluded from analysis. All other subjects received intravenous infusions of CYP-001 on days 0 and 7, at a dose level of either 1 × 10⁶ cells per kg body weight, to a maximum of 1 × 10⁸ cells per infusion (cohort A), or 2 × 10⁶ cells per kg body weight, to a maximum dose of 2 × 10⁸ cells per infusion (cohort B). The primary objective was to assess the safety and tolerability of CYP-001, while the secondary objectives were to evaluate efficacy based on the proportion of participants who showed a complete response (CR), overall response (OR) and overall survival (OS) by days 28/100. CYP-001 was safe and well tolerated. No serious adverse events were assessed as related to CYP-001. OR, CR and OS rates by day 100 were 86.7, 53.3 and 86.7%, respectively. The therapeutic application of iPSC-derived MSCs may now be explored in diverse inflammatory and immune-mediated diseases.

供体来源的间充质基质细胞 (MSC) 的治疗潜力已在多种疾病中得到研究¹，包括类固醇耐药的急性移植物抗宿主病 (SR-aGvHD) ²。然而，传统的制造方法受到可扩展性和供体间差异性挑战的阻碍，临床试验显示出不一致的结果^3,4。诱导多能干细胞 (iPSC) 具有克服这些挑战的潜力，因为它们具有多向分化和无限增殖的能力^5,6. 尽管如此，以前尚未完成 iPSC 衍生细胞的人体临床试验。CYP-001（iPSC 衍生的 MSC）是使用优化的、符合良好生产规范 (GMP) 的制造工艺生产的。我们在 SR-aGvHD 受试者中进行了 1 期开放标签临床试验（编号 NCT02923375）。筛选了 16 名受试者并按顺序分配到队列 A 或队列 B（ 每组n = 8）。队列 B 中的一名受试者在接受 CYP-001 之前退出并被排除在分析之外。所有其他受试者在第 0 天和第 7 天接受 CYP-001 静脉输注，剂量水平为每公斤体重 1 × 10 ^{6 个}细胞，每次输注最多 1 × 10 ^{8 个}细胞（队列 A），或 2 × 10 ⁶每千克体重的细胞，每次输注最大剂量为 2 × 10 ^{8 个}细胞（队列 B）。主要目标是评估 CYP-001 的安全性和耐受性，而次要目标是根据显示完全反应 (CR)、总体反应 (OR) 和总体生存 (OS) 的参与者比例评估疗效第 28/100 天。CYP-001 是安全且耐受性良好的。没有评估与 CYP-001 相关的严重不良事件。第 100 天的 OR、CR 和 OS 率分别为 86.7、53.3 和 86.7%。现在可以探索 iPSC 衍生的 MSC 在多种炎症和免疫介导疾病中的治疗应用。