A Tregs insufficiency is central to autoimmune and inflammatory diseases pathophysiology and low dose interleukin-2 (IL-2) can specifically activate Tregs. To assess IL-2 therapeutic potential and select diseases for further clinical development, we performed an open-label, phase 2a, disease-finding, “basket trial” involving patients with one of 13 different autoimmune diseases. 81 patients treated with IL-2 (1 million IU/day) for 5 days, followed by fortnightly injections. The first 48 patients received diluted Proleukin®, while the subsequent 33 received ready-to-use ILT-101®. The primary endpoint was the change in Tregs at day-8 compared to baseline. Key secondary endpoints included clinical efficacy assessments using the Clinical Global Impression (CGI) scale, disease-specific scores, and EuroQL-5D-5L. Our study unveiled a universal and significant expansion and activation of Tregs, without concomitant Teffs activation, across all 13 autoimmune diseases. Both Proleukin® and ready-to-use ILT-101® demonstrated identical effects on Tregs. CGI scores reflecting activity, severity, and efficacy were significantly reduced in the overall patient population. Disease-specific clinical scores improved in five of the six disease cohorts with at least six patients, namely ankylosing spondylitis, systemic lupus erythematosus, Behçet's disease, Sjögren's syndrome, and systemic sclerosis. Urticaria was the only severe adverse event related to treatment. IL-2 was well-tolerated, exhibiting specific Treg activation and clinical improvements across the 13 autoimmune diseases. Tregs stimulation by IL-2 is a promising therapeutic strategy and IL-2 holds considerable promise for integration into combinatorial therapeutic approaches.

中文翻译：

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篮子临床试验中低剂量 IL-2 对 13 种自身免疫性疾病的普遍影响

Tregs 不足是自身免疫和炎症性疾病病理生理学的核心，低剂量白细胞介素 2 (IL-2) 可以特异性激活 Tregs。为了评估 IL-2 的治疗潜力并选择疾病进行进一步的临床开发，我们进行了一项开放标签、2a 期疾病发现“篮子试验”，涉及患有 13 种不同自身免疫性疾病之一的患者。 81 名患者接受 IL-2（100 万国际单位/天）治疗 5 天，然后每两周注射一次。前 48 名患者接受了稀释的 Proleukin®，而随后的 33 名患者则接受了即用型 ILT-101®。主要终点是第 8 天时与基线相比的 Tregs 变化。主要次要终点包括使用临床总体印象 (CGI) 量表、疾病特异性评分和 EuroQL-5D-5L 进行的临床疗效评估。我们的研究揭示了在所有 13 种自身免疫性疾病中，Treg 细胞普遍且显着的扩增和激活，而无需伴随 Teffs 激活。 Proleukin® 和即用型 ILT-101® 对 Tregs 表现出相同的效果。反映活动、严重程度和疗效的 CGI 评分在整个患者群体中显着降低。在至少有 6 名患者的 6 个疾病队列中，有 5 个队列的疾病特异性临床评分有所改善，即强直性脊柱炎、系统性红斑狼疮、白塞氏病、干燥综合征和系统性硬化症。荨麻疹是唯一与治疗相关的严重不良事件。 IL-2 具有良好的耐受性，在 13 种自身免疫性疾病中表现出特异性 Treg 激活和临床改善。 IL-2 刺激 Tregs 是一种有前景的治疗策略，IL-2 有望整合到组合治疗方法中。