Ulcerative colitis (UC) is a refractory disease characterized by symptoms such as diarrhea, bloody stools, and abdominal pain with repeated relapses and remissions.

开始日期2023-08-01

申办/合作机构

Beni-Suef University

100 项与制瘤素m 相关的临床结果

登录后查看更多信息

100 项与制瘤素m 相关的转化医学

登录后查看更多信息

100 项与制瘤素m 相关的专利（医药）

登录后查看更多信息

470

项与制瘤素m 相关的文献（医药）

2026-06-01·PAIN

Oncostatin M promotes chronic pain through direct regulation on nociceptors in rats

Article

作者: Uhelski, Megan L. ; Abercrombie, Taylor J. ; Elahi, Hajira ; Corrales, German ; Sheffield, Katherine N. ; Li, Yan ; Marri, Tejaswi ; Dougherty, Patrick M. ; North, Robert Y. ; Price, Theodore J.

Abstract:

Oncostatin M (OSM), a member of the interleukin 6 (IL-6) pro-inflammatory cytokine family, is upregulated in the dorsal root ganglia of patients with neuropathic pain and thus may be an important contributor to this condition. Although suggested to contribute to itch in mice, the effects of OSM on nociceptive behavior and nociceptors in rats remain undefined. Here we show that a singular intrathecal dose of OSM (10 ng) induces significant mechanical hypersensitivity in both sexes of rats, yet does not alter thermal withdrawal latencies. When applied to cultured rat dorsal root ganglion (DRG) neurons, OSM (10 ng/mL) elicited robust action potential discharges and exaggerated fluctuations in membrane potential that was not mitigated by an IL-6 receptor antagonist. Neurons reactive to OSM typically did not respond to capsaicin, aligning with the behavioral observations. Immunohistochemical analysis revealed frequent co-localization of OSM and its receptor (OSMR) with isolectin B4–positive and calcitonin gene–related peptide–positive DRG neurons, but only scarce co-localization in transient receptor potential vanilloid 1–positive DRG neurons. In a model of paclitaxel chemotherapy–induced peripheral neuropathy, there is a notable increase in DRG neurons expressing OSM or its receptor (OSMR), alongside an upsurge in several OSM/OSMR downstream signaling molecules. These findings suggest that OSM acts as a signal for mechanical nociception and that heightened OSM expression and OSMR signaling in the DRG may be a key factor in the sensitization of specific nociceptor subsets. Consequently, targeting the OSM/OSMR pathway may offer a promising avenue for treatment in particular neuropathic pain phenotypes.

2026-05-01·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Oncostatin M promotes immune escape, invasion, and metastasis of pancreatic cancer by upregulating PD-L1 via the PI3K/AKT pathway

Article

作者: Jiang, Haixing ; Wei, Xueyan ; Ning, Jing ; Li, Qing ; Zhang, Weiwei ; Chen, Xiubing ; Li, Huazhen

Pancreatic cancer is characterized by rapid progression and high mortality, while the overall benefit of immune checkpoint inhibitors remains limited, highlighting the need for more effective immunotherapeutic strategies. Through bioinformatic screening and clinical tissue analyses, we found that oncostatin M (OSM) expression is closely associated with both PD-L1 levels and tumor metastasis in pancreatic cancer, suggesting its potential as a novel immunotherapeutic target. Western blot (WB), qPCR, and flow cytometry demonstrated that OSM markedly upregulates PD-L1 expression at both the transcriptional and protein levels in pancreatic cancer cells. In a pancreatic cancer cell-PBMC co-culture model, CFSE proliferation assays, intracellular flow cytometry, ELISA, and LDH release assays showed that OSM significantly suppresses CD8⁺ T-cell proliferation, activation, effector cytokine secretion, and cytotoxicity. Meanwhile, wound-healing and Transwell assays revealed enhanced migratory and invasive capacities of pancreatic cancer cells in the presence of OSM. Notably, PD-L1 neutralizing antibodies effectively reversed OSM-induced immunosuppression and tumor cell migration and invasion. Mechanistically, WB analysis indicated that OSM upregulates PD-L1 expression via activation of the PI3K/AKT axis, and the PI3K inhibitor LY294002 abrogated the OSM-driven immunosuppressive and promigratory phenotypes. In vivo imaging, immunofluorescence, and hematoxylin-eosin (HE) staining further confirmed that OSM promotes tumor growth and metastasis, elevates PD-L1 expression, reduces immune infiltration, and suppresses the production of key effector cytokines such as IFN-γ. Collectively, our findings demonstrate that OSM enhances PD-L1 expression through the PI3K/AKT pathway, thereby facilitating immune evasion and metastatic progression in pancreatic cancer, and reveal a potential therapeutic window for immunomodulatory intervention.

2026-04-03·BIOMARKERS

Diagnostic significance of the combination of serum CCL20 and Oncostatin M for early-stage endometrial cancer

Article

作者: Lv, Xiaojuan ; Tang, Huan ; Wei, Yuhua ; Han, Liping ; Zhu, Xiaohong ; Sun, Yeliang ; Chen, Li

AIM:

Our study aimed to preliminarily investigate the role of combined detection of serum CCL20 and Oncostatin M in the diagnosis of early-stage endometrial cancer (EC).

METHODS:

A retrospective study was conducted on 109 patients with early-stage EC. Serum CCL20 and Oncostatin M levels were determined, and their correlations with sex hormone indicators (TTE and DHEAS) in EC patients were analyzed. Influencing factors for EC and the early diagnostic value of each indicator were analyzed.

RESULTS:

Serum CCL20 and Oncostatin M were high in EC patients and positively correlated with TTE and DHEAS. Elevated CCL20 and Oncostatin M were independent risk factors for EC. The diagnostic efficacy of serum CCL20 + Oncostatin M in combination was better than that of serum CCL20, Oncostatin M, CA125, and HE4 alone. The diagnostic test combining serum CCL20 and Oncostatin M in endometrioid carcinoma demonstrated an AUC of 0.855, with a sensitivity of 68.00% and a specificity of 92.86%, comparable to that in the whole early-stage endometrial carcinoma group (AUC = 0.867).

CONCLUSION:

Combined detection of serum CCL20 and Oncostatin M may offer a promising adjunctive approach for the diagnosis of early-stage EC, with their levels correlated to sex hormones and clinicopathological characteristics.

项与制瘤素m 相关的新闻（医药）

2026-07-25

·IBD的冷冻电镜

单基因合集（五）Nat Commun|IF=18.1 TREM1 信号通路可放大炎症性肠病中由中性粒细胞介导的炎症反应

期刊：Nature Communications（IF≈17.6）研发单位：罗氏基因泰克 Genentech 团队关键词：炎症性肠病、IBD、溃疡性结肠炎 UC、TREM1、中性粒细胞、巨噬细胞、菌群 Blautia faecis、治疗耐药、生物标志物、炎症正反馈一、开篇痛点目前临床主流 TNF、IL23、整合素单抗用于溃疡性结肠炎，仅 20%-30% 患者能实现诱导缓解，超半数 1 年内失效，治疗抵抗始终是 IBD 临床最大难题。大量临床队列证实：病灶大量浸润的中性粒细胞是药物无应答核心特征，但中性粒细胞持续过度活化的分子环路长期无人阐明。本研究罗氏 Genentech 团队打通「菌群 - 中性粒细胞 - 单核细胞」三重炎症链条，首次定义两套 TREM1 驱动的正反馈放大环路：中性粒细胞自分泌配体自我激活、单核细胞趋化招募更多中性粒细胞；同时发现肠道共生菌Blautia faecis是人体 TREM1 特异性激活源，血清 sTREM1、血液 PGLYRP1 可作为 UC 活动度 & 用药耐药分层标志物，TREM1 中和抗体具备全新 IBD 治疗潜力，机制 + 临床标志物 + 候选药物三位一体，免疫、肠道菌群、消化疾病方向均可复刻高分课题。二、研究背景临床痛点：中性粒细胞大量浸润的 UC 患者对抗 TNF、维得利珠单抗等药物应答极差，缺少靶向中性粒细胞上游核心通路疗法； TREM1 基础功能：髓系细胞特异性膜受体，结合 PGLYRP1 - 肽聚糖（PGN）复合物启动炎症级联，既往仅知晓促炎，但完整放大环路未知；物种关键差异：人源 PGLYRP1 可二聚化结合 TREM1 激活通路，小鼠 PGLYRP1 为单体无法结合，传统基因敲除小鼠无法模拟人源通路，本研究采用激动抗体绕开物种限制构建结肠炎模型；菌群空白：何种肠道共生菌能激活人 TREM1 未被报道，本研究筛选出Blautia faecis特异性激活人髓系细胞 TREM1，破坏上皮屏障；科学核心问题：TREM1 如何形成持续炎症放大环路？肠道共生菌是否调控该通路？TREM1 通路能否作为 UC 预后、用药预测标志物？靶向 TREM1 能否缓解结肠炎？三、整体研究全流程核心科学问题中性粒细胞激活后分泌 PGLYRP1，是否形成 TREM1 自放大环路？ TREM1 激活的单核细胞是否分泌趋化因子，招募更多中性粒细胞形成二级炎症环路？肠道共生菌Blautia faecis能否通过肽聚糖激活人 TREM1、损伤肠道上皮屏障？ TREM1 通路活性是否与 UC 疾病活动、生物制剂治疗耐药相关？体内激活 / 阻断 TREM1 能否调控小鼠肠道炎症严重程度？完整实验逻辑链人中性粒细胞分泌组蛋白质组筛选 TREM1 配体 PGLYRP1→体外细胞验证第一重中性粒细胞自反馈环路→单核细胞转录组解析第二重跨细胞趋化放大环路→共生菌筛选找到Blautia faecis，验证其 PGN 依赖激活人 TREM1→Transwell 共培养上皮 / 髓细胞证实菌群 - TREM1 破坏屏障→小鼠 TREM1 激动抗体 DSS 造模验证体内促炎作用→7 套公共 IBD 临床队列（911 例）验证 TREM1 通路 signature、sTREM1、PGLYRP1 临床预测价值。全套实验技术清单蛋白质组学：PMA 激活人中性粒细胞上清 TMT 标记质谱，筛选分泌差异蛋白；体外髓系细胞实验：人原代中性粒细胞、单核细胞分离；TREM1 激动 / 中和抗体干预；ROS、NETosis、脱颗粒 CD63、趋化实验；转录组：TREM1 激活单核细胞 RNA-seq，GSEA 富集趋化 / 促炎通路；细菌筛选：15 株肠道共生菌上清 TREM1 荧光素酶报告细胞筛选；PGN、溶菌酶干预验证激活依赖肽聚糖；免疫荧光验证 PGLYRP 结合Blautia faecis菌体；上皮屏障模型：Caco2 单层 Transwell，TEER 电阻检测屏障完整性；髓细胞 + 细菌共培养模拟肠道微环境；体内动物实验：小鼠多价 TREM1 激动抗体 muTREM1.MVago 干预 DSS 结肠炎；体重、DAI、结肠长度、流式髓系 / Th17、组织炎症因子检测；临床多组学分析：7 个 GEO 公共 IBD 队列 ssGSEA 计算 TREM1 通路得分；单 / 多中心患者血清 sTREM1、外周血 PGLYRP1 qPCR；组织原位杂交 TREM1 定位；分子互作：SPR 表面等离子共振验证人 / 鼠 PGLYRP1-TREM1 结合物种差异。四、分层核心结果3.1 图 1：中性粒细胞分泌 PGLYRP1，构建 TREM1 自我放大正反馈环路 PMA / 大肠杆菌激活中性粒细胞分泌组质谱：PGLYRP1、TREM1、MPO 等炎症蛋白显著上调；免疫荧光显示 PGLYRP1 储存在中性粒细胞颗粒内；功能验证：PGLYRP1 联合细菌 PGN 可激活 TREM1，进一步促进中性粒细胞持续分泌更多 PGLYRP1，形成自放大循环； TREM1 激活后显著诱导中性粒细胞脱颗粒（CD63 膜定位上升）、ROS 大量生成、NETs 释放（MPO-DNA 复合物升高）；TREM1 中和抗体可完全阻断上述炎症表型；结论：中性粒细胞被刺激后释放配体 PGLYRP1，持续激活自身 TREM1，不断放大局部炎症损伤。图1 中性粒细胞自放大环路实验图3.2 图 2：TREM1 激活单核细胞分泌趋化因子，形成第二重跨细胞炎症放大环路 TREM1 激动抗体 / PGN-PGLYRP1 复合物刺激单核细胞转录组：大量中性粒细胞趋化因子 IL8、CCL20，促炎细胞因子 TNF、TL1A、IL23 显著上调；上清功能实验：TREM1 激活单核细胞培养上清可强效诱导中性粒细胞 ROS 生成、趋化迁移；中和 IL8 可完全抑制趋化效应，中和 TNF 阻断 ROS；通路串联：单核细胞分泌 IL23/TL1A 驱动 Th17 分化，Th17 释放 IL17 进一步刺激内皮分泌趋化信号，招募更多中性粒细胞浸润病灶；结论：单核细胞 TREM1 活化后释放趋化因子，源源不断招募外周中性粒细胞进入肠道，持续扩增炎症规模。图2 单核-中性粒细胞交叉激活机制图3.3 图 3：肠道共生菌Blautia faecis肽聚糖特异性激活人 TREM1，破坏肠道上皮屏障人 / 鼠 TREM 报告细胞筛选 15 株肠道共生菌：仅Blautia faecis上清可特异性激活人 TREM1，对小鼠 TREM 无激活作用；溶菌酶降解细菌 PGN 后激活效应完全消失；分子结合实验：重组人 PGLYRP1 可直接结合Blautia faecis菌体表面；活菌联合 PGLYRP1 刺激髓细胞，显著提升 TNF、ROS 释放，TREM1 阻断后效应消失； Caco2 上皮 TEER 屏障实验：单独细菌无损伤；单核 + 中性粒细胞共培养体系中加入Blautia faecis，TREM1 依赖式大幅降低上皮电阻、破坏黏膜屏障；结论：肠道紊乱富集的Blautia faecis，通过肽聚糖 - PGLYRP1-TREM1 通路触发髓细胞炎症，摧毁肠道上皮屏障，菌群与免疫形成恶性循环。图3 Blautia faecis激活TREM1屏障实验图3.4 图 4：体内激活 TREM1 显著加重DSS诱导小鼠结肠炎物种差异前置验证：人 PGLYRP1 可结合人 TREM1，但小鼠 PGLYRP1 单体无法结合鼠 TREM1，无天然配体，因此开发多价鼠 TREM1 激动抗体 muTREM1.MVago 造模； DSS 结肠炎给药表型：激动抗体处理小鼠体重下降更快、结肠显著缩短、结肠重量长度比值升高，肠道髓系细胞（巨噬 / 中性粒细胞）大量浸润；组织分子检测：结肠趋化因子 CCL2/4/5、促炎 TNF、G-CSF、Th17 相关 IL17A 全面升高；结论：TREM1 通路持续激活会在体内加剧肠道黏膜炎症，是结肠炎加重关键驱动因子。图4 小鼠体内结肠炎动物结果图3.5 图 5：TREM1 通路高表达是 UC 活动、生物制剂耐药标志性特征 ssGSEA 通路评分：7 套共 911 例 IBD 公共队列，CD、UC 患者病灶 TREM1 通路 signature 显著高于健康人，炎症病灶远高于自身非炎症黏膜；耐药分层：仅溃疡性结肠炎（UC）中，TREM1 通路高表达患者对抗 TNF、维得利珠单抗等生物制剂应答差，克罗恩病无此关联；临床样本验证：UC 患者血清 sTREM1 浓度、外周血 PGLYRP1 mRNA 显著高于健康人，且与 Mayo 活动评分、便血、粪乳铁蛋白正相关；结肠组织原位杂交显示溃疡区域 TREM1 转录信号显著升高；临床转化结论：检测外周 PGLYRP1、血清 sTREM1 可评估 UC 活动度，TREM1 通路高表达患者需更换中性粒细胞靶向治疗方案。图5 临床队列标志物分析图五、文章总结 & 课题复刻指南五大核心创新双重炎症正反馈新机制首次完整定义 TREM1 两套放大环路 —— 中性粒细胞自分泌 PGLYRP1 自我激活、单核细胞趋化招募中性粒细胞，解释 IBD 慢性持续炎症根源；人特异性菌群靶点发现共生菌Blautia faecis肽聚糖是人体 TREM1 天然激活配体，打通肠道菌群 - 髓系免疫 - 黏膜损伤完整链条；物种机制差异突破阐明人 / 鼠 PGLYRP1-TREM1 结合区别，解决传统敲除小鼠无法模拟人通路难题，为 TREM1 抗体临床前模型提供方案；临床分层标志物 sTREM1、PGLYRP1、TREM1 通路 signature 三重标志物，可预判 UC 疾病严重程度与生物制剂治疗耐药；全新药物靶点 TREM1 中和抗体可阻断整条炎症放大轴，区别现有单一细胞因子单抗，为耐药 UC 提供全新治疗赛道。课题复刻梯度 & 成本参考低配（硕士毕业）：人中性粒细胞体外 TREM1 功能验证 + DSS 小鼠激动抗体表型；中配（二区 SCI）：增加细菌筛选、Caco2 屏障 TEER、少量临床样本 qPCR 验证；顶配（Nat Comm/Gut 级别）：中性粒细胞蛋白质组、单核 RNA-seq、SPR 分子互作、多中心临床队列生信分析。三大临床转化价值诊断分层肠镜活检、外周血 PGLYRP1、血清 sTREM1 可作为 UC 无创活动度检测指标；用药预判初诊 UC 检测 TREM1 通路活性，高表达患者优先选用 TREM1 中和类候选药物，避免单抗无效；新药开发 TREM1 阻断型单克隆抗体，同时抑制中性粒细胞、单核细胞双重炎症环路，解决现有药物仅阻断单一细胞因子、中性粒细胞浸润持续耐药痛点。编者注：这篇文章只有5个大Figure，与常见的机制文章差异很大，基质做得也不深，但能发NC，原因还是跟生物制剂治疗无效相关，多队列验证TREM1 通路高表达是 UC 活动、生物制剂耐药标志性特征。跟2017年发表在《Nature Medicine》的Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor–neutralizing therapy in patients with inflammatory bowel disease. 有异曲同工之处。六、科研交流：做 IBD、中性粒细胞、髓系免疫、肠道菌群的同行，TREM1 物种差异动物模型构建难点欢迎留言讨论！资料福利：后台回复【TREM1-IBD】领取本文全套原图 + 完整实验方法 + 公共队列 GEO 编号；下期预告：拆解另一篇基质细胞介导 IBD 耐药顶刊论文。

2026-07-21

·人福医药研究院

人福医药治疗瘙痒创新药注射用HWS113 Ⅰ期临床研究完成首例受试者入组

近日，人福医药自主研发的IL-31RA人源化单克隆抗体注射用HWS113 Ⅰ期临床试验顺利完成首例受试者入组，标志着该产品正式进入人体试验阶段。这项“在健康研究参与者中评价注射用HWS113单次给药的安全性、耐受性、免疫原性及药代动力学特征的I期、随机、双盲、单中心、剂量递增、安慰剂对照临床研究”，由山东第一医科大学第一附属医院赵维主任牵头，目的是在健康研究参与者中评价注射用HWS113单次皮下给药的安全性、耐受性、药代动力学特征和免疫原性。关于IL-31RA单抗白细胞介素-31（IL-31）归属于IL-6细胞因子家族，亦被称作“致痒细胞因子”。该因子主要由活化Th2细胞与角质形成细胞分泌，是结节性痒疹、特应性皮炎等Th2型炎症皮肤病发病过程中调控瘙痒的核心介质。IL-31可与感觉神经元表面异源二聚体受体IL-31RA/OSMRβ相结合，启动下游JAK/STAT、PI3K/AKT及MAPK信号通路，向中枢传导痒觉信号，诱发剧烈瘙痒[1]。与此同时，IL-31可促进感觉神经纤维增生与轴突延伸，降低皮肤痒觉阈值，造成外周神经敏化，使瘙痒迁延为慢性病程。 IL-31除主导痒觉传导外，还深度参与Th2型炎症进程。该因子可刺激角质形成细胞、巨噬细胞释放各类促炎细胞因子与趋化因子，募集并活化免疫细胞，放大局部炎症反应；还可抑制角质形成细胞正常分化，破坏皮肤屏障稳态，进一步促使表皮细胞大量释放炎症介质与致痒物质，形成瘙痒-炎症恶性循环。此外，IL-31可作用于真皮成纤维细胞，诱导胶原合成与炎症因子分泌，启动皮肤组织纤维化重塑进程[2]。临床标本检测显示，IL-31在特应性皮炎、结节性痒疹等多种瘙痒性皮肤病皮损中表达显著升高，其中结节性痒疹病灶内IL-31 mRNA表达水平可上调至正常组织的50倍以上[3]。特异性阻断 IL-31RA，既可直接切断痒觉信号传导，又能下调下游Th2、Th17介导的炎症应答，抑制神经生长因子（NGF）引发的神经元功能异常，并逆转角质形成细胞过度增殖与促纤维化通路异常激活[4]。慢性瘙痒是指瘙痒症状持续时间大于6周，涵盖各类病因引发的顽固性瘙痒病症。该病人群患病率较高，可显著损害患者躯体健康与心理健康，现阶段仍缺少疗效确切的干预方案。以IL-31RA为作用靶点的单克隆抗体具备高度靶向特异性，可精准阻断痒觉信号通路的传导，在提升临床疗效、降低全身性不良反应方面具备突出优势。截至目前，国内暂未有针对IL-31RA靶点的治疗药物获批上市。关于HWS113 HWS113是由人福医药自主研发、靶向IL-31RA的全新人源化单克隆抗体。本品对IL-31RA具备高结合亲和力，可强效阻断IL-31信号通路。动物药效试验结果显示，该药物可明显改善瘙痒与炎症症状，药效优于境外已上市同靶点同类产品。本品不干扰IL-31家族其他细胞因子（IL-6、抑瘤素M）介导的信号通路，同时常规毒性试验、局部刺激性试验与免疫毒性试验结果均提示药物毒性水平低，整体安全性良好。注射用HWS113系国内首个进入临床试验阶段的IL-31RA靶向单克隆抗体药物。随着研发进程稳步推进，该药物有望早日落地临床，为慢性瘙痒患者开辟精准治疗新路径，弥补当前临床有效治疗药物不足的现状。关于人福医药研究院人福医药研究院是人福医药集团的中央研发机构，是集团创新发展的核心引擎，承载着集团战略转型使命，为构建全球研发体系、冲刺世界一流生命科技企业提供核心支撑。研究院聚焦创新药研发，以满足未被满足的临床需求为导向，在集团的优势治疗领域持续深耕，凭借强劲的自主研发与转化能力确立和巩固集团在核心细分赛道的研发优势。研究院将以患者需求为初心、科技创新为引擎，深耕生命健康领域，用优质创新药物赋能人类健康事业，助力集团打造全球竞争力。如需了解更多研发动态，欢迎关注“人福医药研究院”微信公众号。 First Subject Enrolled in Phase Ⅰ Trial of Humanwell Healthcare’s HWS113 for Pruritus Humanwell Healthcare has successfully dosed the first subject in the Phase Ⅰ clinical trial of HWS113, an investigational humanized monoclonal antibody against IL-31RA. The Phase Ⅰ, randomized, double-blind, single-center, dose-escalation, placebo-controlled study of HWS113 has been initiated under the leadership of Principal Investigator Dr. Wei Zhao at the First Hospital Affiliated with Shandong First Medical University. The trial is designed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of a single subcutaneous dose of HWS113 in healthy volunteers. About Anti-IL-31 Receptor Antibody Interleukin-31 (IL-31), a member of the IL-6 cytokine family, has been characterized as a pruritogenic cytokine. It is primarily secreted by activated Th2 cells and keratinocytes and acts as a key itch mediator in Th2-type inflammatory skin diseases such as prurigo nodularis and atopic dermatitis. IL-31 binds to the heterodimeric receptor IL-31RA/OSMRβ on sensory neurons, activating downstream JAK/STAT, PI3K/AKT, and MAPK signaling pathways. This relays itch signals to the central nervous system and elicits intense pruritus[1]. Moreover, IL-31 promotes sensory nerve fiber sprouting and axonal elongation, lowers the cutaneous itch threshold, and induces peripheral sensitization, thereby driving the chronification of pruritus. Beyond its central role in itch signaling, IL-31 is critically involved in Th2-type inflammatory processes. It stimulates keratinocytes and macrophages to release various pro-inflammatory cytokines and chemokines, which recruit and activate immune cells, amplifying local inflammatory responses. IL-31 also inhibits normal keratinocyte differentiation and disrupts skin barrier homeostasis, further promoting the excessive release of inflammatory mediators and pruritogens from epidermal cells, thereby perpetuating an itch-inflammation vicious cycle. Furthermore, IL-31 acts on dermal fibroblasts to induce collagen synthesis and the secretion of pro-inflammatory cytokines, initiating cutaneous fibrosis and tissue remodeling[2]. Analysis of clinical specimens has shown that IL-31 expression is significantly elevated in skin lesions of various pruritic dermatoses, including atopic dermatitis and prurigo nodularis. Notably, IL-31 mRNA levels in prurigo nodularis lesions can be upregulated by more than 50-fold relative to normal tissue[3]. Specific blockade of IL-31RA not only directly interrupts itch signaling, but also downregulates Th2- and Th17-mediated inflammatory responses, inhibits neuronal dysfunction induced by nerve growth factor (NGF), and suppresses keratinocyte hyperproliferation and aberrant activation of pro-fibrotic pathways[4]. Chronic pruritus is defined as itch lasting more than six weeks, encompassing a range of refractory pruritic disorders arising from various etiologies. The condition is highly prevalent in the general population and can significantly impair patients' physical and mental health. At present, effective treatment options remain limited. Anti-IL-31 Receptor Antibody are highly target-specific, allowing precise blockade of itch signaling pathway, and offer distinct advantages in both clinical efficacy and the reduction of systemic adverse effects. To date, no anti-IL-31 receptor antibody has been approved for marketing in China. About HWS113 HWS113 is a novel, humanized anti-IL-31 receptor monoclonal antibody, independently developed by Humanwell Healthcare. The antibody exhibits high binding affinity for IL-31RA and potently blocks the IL-31 signaling pathway. In vivo pharmacodynamic studies have shown that HWS113 significantly relieves pruritus and inflammation, demonstrating superior efficacy compared to anti-IL-31RA therapies currently marketed outside China. Importantly, HWS113 does not interfere with the signaling pathways mediated by other members of the IL-6 cytokine family, such as IL-6 and Oncostatin M. Furthermore, results from general toxicology, local irritation, and immunotoxicity studies have collectively demonstrated a favorable overall safety and low-toxicity profile. HWS113 is the first anti-IL-31RA monoclonal antibody to enter clinical trials in China. As its clinical development steadily advances, HWS113 is poised to offer a novel precision treatment option for patients suffering from chronic pruritus, addressing a significant unmet medical need. About Humanwell R&D Institute Humanwell Pharmaceutical Research and Development Institute is the central R&D organization of Humanwell Healthcare and the core engine driving Humanwell's innovation-led development. It undertakes Humanwell's strategic transformation mission and provides essential support for building a global R&D system and advancing toward a world-class life sciences enterprise. Focused on innovative drug development and guided by unmet clinical needs, the Institute continues to deepen its expertise in Humanwell's key therapeutic areas, leveraging strong in-house R&D and translational capabilities to establish and reinforce Humanwell's research advantages in core niche segments. With patient needs as its founding mission and technological innovation as its driving force, the Institute is committed to advancing the field of life and health sciences, empowering human health through high-quality innovative medicines, and helping Humanwell build global competitiveness. For more updates on our R&D progress, follow the official WeChat account "Humanwell Pharmaceutical Research Institute". 参考文献： [1]Datsi A, Steinhoff M, Ahmad F, et al. Interleukin-31: The "itchy" cytokine in inflammation and therapy. Allergy. 2021 Oct;76(10):2982-2997. [2]Nemmer JM, Kuchner M, Datsi A, et al. Interleukin-31 Signaling Bridges the Gap Between Immune Cells, the Nervous System and Epithelial Tissues. Front Med (Lausanne). 2021 Feb 10;8:639097. [3]Sonkoly E, Muller A, Lauerma AI, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006 Feb;117(2):411-7. [4]Tsoi LC, Hacini-Rachinel F, Fogel P, et al.. Transcriptomic characterization of prurigo nodularis and the therapeutic response to nemolizumab. J Allergy Clin Immunol. 2022 Apr;149(4):1329-1339. 声明： 1. 本资讯旨在分享医药领域的科研进展与前沿信息，仅供医疗卫生专业人士进行学术交流与参考，不构成任何广告或产品推荐。 2. 本资讯中涉及的信息不能替代专业医疗指导，所有医疗决策请遵从医疗卫生专业人士的意见或指导。 3. 本资讯任何前瞻性陈述均基于当前预测，实际结果可能存在不确定性。 4. 对于依赖本文信息作出的任何决定或行动，本公司不承担相关责任。

2026-07-15

·医脉通消化科

首个TL1A药物取得阳性结果，与抗TNF效果对比如何？

导语 2026年6月22日，肿瘤坏死因子样配体1A（TL1A）靶点药物Tulisokibart宣布在三期ATLAS-UC诱导研究中达到主要终点，这是抗TL1A这一全新机制类别在全球范围内的第一个三期阳性读出。对一个全新的治疗靶点而言，这是分水岭式的一刻。然而对比其他机制通路药物，TL1A的效果是否有明显优势？在刚刚结束的第14届亚洲炎症性肠病组织年会（AOCC 2026）上，一项基于TUSCANY-2和HIBISCUSI/II数据的间接比较研究为这一问题提供了有力的数据支持1：在抗肿瘤坏死因子（TNF）初治的中重度溃疡性结肠炎（UC）患者中，靶向TL1A药物Afimkibart在临床缓解与内镜改善终点上的疗效显著优于阿达木单抗，临床应答与内镜缓解同样呈现获益趋势。医脉通特邀请摘要作者中山大学附属第六医院高翔教授，解读这项间接比较研究的临床意义，以及其背后TL1A的独特双效机制。间接头对头数据公布，Afimkibart临床与内镜获益优于阿达木单抗1 研究设计：倾向评分匹配模拟头对头效果研究纳入抗TNF初治的中重度UC人群，Afimkibart数据源自TUSCANY-2研究（n=101，50/150/450mg剂量合并），阿达木单抗数据源自HIBISCUSI/II研究（n=273，160 mg SC week 0, 80 mg SC week 2, and 40 mg SC Q2W）。通过倾向评分匹配，校正年龄、性别、基线疾病活动度、病程、激素使用等混杂因素后，最终匹配152例患者，最大程度降低了因不同试验设计导致的基线偏倚。图1 倾向评分匹配核心终点：两项关键指标显著优于阿达木单抗匹配校正前，Afimkibart（TUSCANY-2研究）和阿达木单抗（HIBISCUS I/II研究）的临床缓解率分别为41.6%和26.0%。匹配校正后，Afimkibart较阿达木单抗呈现明确疗效优势：临床缓解：风险差19.7%（95% CI：0.049~0.346，P=0.010）；内镜改善：风险差26.3%（95% CI：0.112~0.415，P=0.001），均具有统计学显著性。次要终点：整体获益趋势高度一致在临床应答与内镜缓解层面，Afimkibart均呈现更优的一致性趋势：临床应答风险差14.5%（95% CI：-0.010~0.300，P=0.067）；内镜缓解风险差10.5%（95% CI：-0.011~0.221，P=0.075）。额外校正年龄、种族、体重指数（BMI）等因素的敏感性分析显示，核心结论保持一致。图2 Afimkibart和阿达木单抗的间接比较注：虚线右侧代表Afimkibart疗效优于阿达木单抗，RD数值越大，获益优势越明显该研究是首个利用临床试验数据和倾向评分法比较Afimkibart与其他生物制剂治疗UC疗效的分析。在缺乏头对头试验的情况下，通过倾向评分校正控制不同研究间的基线协变量差异，得到了稳健的疗效对比结果。总体而言，在生物制剂初治UC患者中，Afimkibart治疗后临床与内镜终点的改善程度均优于阿达木单抗。分子机制探索：从源头遏制炎症级联与纤维化进程 TL1A靶点为何能展现出当前的临床获益？这得益于其区别于传统下游单点阻断的独特双效机制： 1. TL1A靶点：免疫炎症通路的“级联放大器” TL1A与死亡受体3（DR3）结合后会启动炎症级联放大效应，激活单核细胞、巨噬细胞、树突状细胞、内皮及上皮细胞等，进一步促进多种炎症因子分泌、推动组织重塑2。抗TL1A抗体Afimkibart可通过阻断TL1A与DR3的结合，下调炎症通路，抑制相关病理效应3。图3 TL1A-DR3轴放大促炎、促纤维化通路1 2. TL1A通路覆盖：同步调控免疫活化与纤维化通路 ECCO 2026公布的TUSCANY-2血清蛋白质组学研究验证，Afimkibart治疗14周可显著下调45种相关蛋白，覆盖适应性免疫活化、髓系细胞反应、基质组织重塑三大病理模块，突破了单一抗炎靶点的作用边界，展现出作为新型“疾病修饰治疗”的巨大应用潜力5。图4 第14周血清蛋白水平 3. 覆盖非TNF依赖通路，破局抗TNF原发无应答困境抗TNF原发无应答是IBD临床治疗中的棘手问题，提示部分患者的疾病活动可能并非主要由TNF-α通路驱动。既往研究提示，抑瘤素M（OSM）炎症通路可通过髓系细胞和基质细胞相关信号放大局部炎症反应，与抗TNF治疗反应不佳及黏膜持续炎症密切相关 6.7。TUSCANY-2相关蛋白质组学结果提示，Afimkibart治疗后显著下调包括OSM在内的多种非TNF依赖性炎症及组织重塑相关蛋白5。这一发现为TL1A阻断区别于TNF-α阻断提供了机制线索，也为对抗TNF疗效不足的患者提供了新的治疗方向。总结基于AOCC 2026公布的间接对比研究，在抗TNF初治的中重度UC人群中，Afimkibart的临床缓解与内镜改善疗效显著优于阿达木单抗，同时在长期阻断炎症级联、逆转肠道纤维化方面具备独特的机制优势。目前，评估Afimkibart用于克罗恩病治疗的Ⅲ期临床研究——SIBERITE1/2研究正在国内和全球范围内积极入组中。Afimkibart可上游阻断炎症级联、调控多重病理通路，覆盖非TNF耐药通路，有望突破传统单抗治疗局限，补足IBD抗炎抗纤维化的临床未满足需求。专家简介高翔教授主任医师、博士研究生导师，消化内科主任亚洲炎症性肠病学组（AOCC）常务理事 AOCC流行病学学组主席中华医学会消化病学分会炎症性肠病学组顾问广东省医师协会炎症性肠病专业委员会主任委员广东省医学会消化病学分会副主委广东省医师协会肝病专科分会副主任委员《中华炎性肠病杂志》青年学术组组长担任人民卫生出版社内科学教材（第九版、第十版）及《中华炎性肠病杂志》编委我们诚邀您参与以下3个前沿学术话题的快速调研：参考文献 1.Xiang Gao, Qixiang Xu, Vishal A. Manickam, Yihao Li, Steven Levitte, Jiameng Zhang. Indirect Comparison of Afimkibart and Adalimumab Treatment Effects Using Data From TUSCANY-2 and HIBISCUS in Patients With Ulcerative Colitis. Aocc 2026. P2-065. 2.Xu WD, Li R, Huang AF. Role of TL1A in Inflammatory Autoimmune Diseases: A Comprehensive Review. Front Immunol. 2022 Jul 14;13:891328. 3.Hassan-Zahraee M, Ye Z, Xi L, et al. Antitumor Necrosis Factor-like Ligand 1A Therapy Targets Tissue Inflammation and Fibrosis Pathways and Reduces Gut Pathobionts in Ulcerative Colitis. Inflamm Bowel Dis. 2022;28(3):434-446. 4.V Jairath, J R Allegretti, A Yarur, S Danese, S Schreiber, L Peyrin-Biroulet, J Kierkus, R W Leong, M S Vincent, A Banerjee, D E Chandra, E Peeva, S Neelakantan, K E Hung, D Bojic, K Lasch, C Schiffman, B Feagan. Treatment with RO7790121 induces and maintains histologic and histologic-endoscopic improvement and remission in moderately to severely active ulcerative colitis – Results from TUSCANY-2. ECCO 2026. OP39 5.S Chang, A Nguyen, J Shim, G Sperinde, A Banerjee, D E Chandra, E Peeva, S Neelakantan, M S Vincent, M Neighbors. Afimkibart downregulates Th17, myeloid, and fibrotic pathways in ulcerative colitis: serum proteomics from the phase 2b TUSCANY-2 trial. ECCO 2026. P0166 6.West NR, Hegazy AN, Owens BMJ, Bullers SJ, Linggi B, Buonocore S, Coccia M, Görtz D, This S, Stockenhuber K, Pott J, Friedrich M, Ryzhakov G, Baribaud F, Brodmerkel C, Cieluch C, Rahman N, Müller-Newen G, Owens RJ, Kühl AA, Maloy KJ, Plevy SE; Oxford IBD Cohort Investigators; Keshav S, Travis SPL, Powrie F. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat Med. 2017 May;23(5):579-589. 7.Yang Y, Fu KZ, Pan G. Role of Oncostatin M in the prognosis of inflammatory bowel disease: A meta-analysis. World J Gastrointest Surg. 2024 Jan 27;16(1):228-238. 本平台旨在为医疗卫生专业人士传递更多医学信息。本平台发布的内容，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。如该等信息被用于了解医学信息以外的目的，本平台不承担相关责任。本平台对发布的内容，并不代表同意其描述和观点。若涉及版权问题，烦请权利人与我们联系，我们将尽快处理。

100 项与制瘤素m 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
免疫缺陷综合征	临床1期	美国	Bristol Myers Squibb Co.	-
肿瘤	临床1期	美国	Bristol Myers Squibb Co.	-
视网膜新生血管形成	临床前	德国	University of Freiburg	2022-05-01