A Phase 3b, 12-month, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of BIIB019, Daclizumab, in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab (SUSTAIN)

The primary objective of the study is to evaluate the effects of treatment with daclizumab on the proportion of participants relapse-free at 6 months in Relapsing-Remitting Multiple Sclerosis (RRMS) participants, who switched from treatment with natalizumab to daclizumab due to safety concerns. The secondary objectives of this study in this study population are to evaluate the effects of daclizumab on the following: 1) Multiple Sclerosis (MS) relapse activity including the annualized relapse rate (ARR) and the proportion of participants experiencing relapses requiring hospitalization and/or steroid treatment; 2) MS-related outcomes measured using magnetic resonance imaging (MRI); 3) Safety and tolerability in participants previously treated with natalizumab.

开始日期2017-04-18

申办/合作机构

Biogen, Inc.

CTRI/2014/04/004551 / Completed临床3期

A Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Safety and Efficacy of BIIB019, Daclizumab High Yield Process (DAC HYP), Monotherapy in Subjects With Multiple Sclerosis Who Have Completed Study 205MS301. - 205MS303

开始日期2014-04-24

申办/合作机构

Biogen MA, Inc.

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100 项与达克珠单抗相关的临床结果

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100 项与达克珠单抗相关的转化医学

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100 项与达克珠单抗相关的专利（医药）

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1,269

项与达克珠单抗相关的文献（医药）

2024-03-01·Carbohydrate polymers

Multi-crosslinked hydrogel built with hyaluronic acid-tyramine, thiolated glycol chitosan and copper-doped bioglass nanoparticles for expediting wound healing

Article

作者: Wang, Congcong ; Yu, Yifeng ; Wan, Ying ; Yu, Aixi ; Fu, Qiaoqin

The migration of fibroblasts and endothelial cells is a critical determinant of wound-healing outcomes for skin injuries. Here, hyaluronic acid-tyramine (HAT) and thiolated glycol chitosan (TGC) conjugates were combined with copper-doped bioglass (ACuBG) nanoparticles to build a novel type of multi-crosslinked hydrogel for stimulating the migration of cells, and thus, expediting wound healing. The optimally devised HAT/TGC/ACuBG gels had markedly improved strength and stiffness compared to the gels built from either HAT or TGC while showing sufficient elasticity, which contributes to stimulating the migration of fibroblasts. The sustainable release of silicon and copper ions from the gels was found to jointly induce the migration of human umbilical vein endothelial cells. The results based on mouse full-thickness skin defects demonstrated that they were able to fully restore the skin defects with formation of complete appendages within two weeks, suggesting their promising potency for use in expediting wound healing.

2024-01-22·Current medicinal chemistry

Therapeutic Role of HAT Therapy in Sepsis: A Systematic Review and Meta-Analysis

Article

作者: Saghafi, Fatemeh ; Boostani Moghadam, Zahra ; Jamialahmadi, Tannaz ; Sohrevardi, Seyed Mojtaba ; Sahebnasagh, Adeleh ; Salehi-Abargouei, Amin ; Sahebkar, Amirhossein ; Beigrezaei, Sara

Background::

This systematic review and meta-analysis aimed to determine whether the combination of hydrocortisone, vitamin C (ascorbic acid), and thiamine (HAT therapy) diminishes the mortality and is effective in expediting the resolution of sepsis and septic shock or not.

Methods::

The following databases of PubMed, Scopus, ISI Web of Science, and Google Scholar were explored until March 2021 for all existing literature related to this field. An automatic alert for all databases was also activated to update our search. Meta-analysis was performed on clinical trials and cohorts separately as well as on all the pooled populations.

Results::

This study evaluated nine clinical trials (1358 participants) and nine cohorts (339,437 participants) and is the most comprehensive systematic review in this field. The results of our meta-analysis demonstrated a significant difference in the reduction of Sepsis-Related Organ Failure Assessment (SOFA) score changes (Δ-SOFA) over 72 h (Standard Mean Difference (SMD) = −0.429; 95% CI: −0.737, 0.120; P = 0.006), duration of vasopressor (VP) (SMD = −0.373; 95% CI: −0.619, −0.128; P = 0.003), and procalcitonin (PCT) clearance (SMD = 0.496; 95% CI: 0.061, 0.931%; P = 0.026). Considering the results of cohorts, HAT therapy was effective in the survival of intensive care units (ICUs) patients (OR = 0.641; 95% CI: 0.423-0.970, P = 0.035). However, no significant difference was observed between the intervention and control groups in hospital mortality (Odds Ratio (OR) = 0.811, 95% CI: 0.544-1.209, P = 0.304), 28- to 30-day mortality (OR = 1.000; 95% CI: 0.782-1.279, P = 0.998), new onset acute kidney injury requiring renal replacement therapy ((OR = 0.856, 95% CI: 0.526, 1.391; P = 0.529), in-hospital length of stay (LOS) (SMD = 0.090; 95% CI: −0.036, 0.216 days; P = 0.162), LOS in ICU (SMD = 0.016, 95% CI: −0.138, 0.170 days; P = 0.838), and mechanical ventilation-free days (SMD = 0.004; 95% CI: −0.154, 0.163 days; P = 0.956).

Conclusion::

Supplementation of septic and septic shock patients with HAT therapy has significant beneficial effects on SOFA score over 72 hours, duration of exogenous vasopressor infusion and procalcitonin clearance. Considering the results of cohort studies, supplementation with HAT is efficacious in reducing ICU mortality.

2024-01-01·Clinical transplantation

Outcomes of kidney transplantation in patients with IgA nephropathy based on induction: A UNOS data analysis

Article

作者: Koizumi, Naoru ; Aydin-Ghormoz, Emmanuel Albert ; Ortiz, Jorge ; Faddoul, Geovani ; Perlmutter, Jason

Abstract:

Introduction:

IgA nephropathy (IgAN) can cause end‐stage kidney disease (ESKD). This study assesses the impact of induction and maintenance immunosuppression on IgAN recurrence, graft survival, and mortality in living and deceased donor kidney transplants (LDKT and DDKT).

Methods:

Retrospective analysis of the UNOS database in adults with ESKD secondary to IgAN who received kidney transplants between January 2000 and June 30, 2022. Patients with thymoglobulin (ATG), alemtuzumab, or basiliximab/daclizumab induction with calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) with or without prednisone maintenance were analyzed. Multivariate logistic regression was performed to identify factors correlated with IgA recurrence. Multivariable Cox regression analyses were performed for clinically suspected risk factors. Kaplan Meir Analysis was utilized for overall graft survival.

Results:

Compared to ATG with steroid maintenance, alemtuzumab with steroid increased the odds of IgAN recurrence in DDKTs (OR 1.90, p < .010, 95% CI [1.169–3.101]). Alemtuzumab with and without steroid increased the odds of recurrence by 52% (p = .036) and 56% (p = .005), respectively, in LDKTs. ATG without steroids was associated with less risk of IgAN recurrence (HR .665, p = .044, 95% CI [.447–.989]), graft failure (HR .758, p = .002, 95% CI [.633–.907]), and death (HR .619, p < .001, 95% CI [.490–.783]) in DDKTs. Recurrence was strongly associated with risks of graft failure in DDKTs and LDKTs and death in LDKTs.

Conclusion:

In patients with IgAN requiring a kidney transplant, Alemtuzumab induction correlates with increased IgAN recurrence. Relapse significantly affects graft survival and mortality. ATG without steroids is associated with the least graft loss and mortality.

项与达克珠单抗相关的新闻（医药）

2024-06-15

·梅斯医学

「亚胺培南 + 万古霉素」都无效的肺炎，最后只用了它就搞定了？

导语社区获得性肺炎(community acquired pneumonia,CAP)是全球主要的传染病负担，是入住ICU的常见病因，指在医院外罹患的感染性肺实质炎症，包括具有明确潜伏期的病原体感染在人院后于潜伏期内发病的肺炎。临床统计约22%～42%的CAP患者需要住院治疗，其中17%～21%的住院患者为重症社区获得性肺炎（SCAP）。SCAP病的原学调查研究表明，SCAP患者最常见的病原体包括肺炎链球菌、流感嗜血杆菌和嗜肺军团杆菌等，在免疫功能低下的患者中，肺孢子菌、肺炎克雷伯菌、肺炎链球菌、流感嗜血杆菌和铜绿假单胞菌是最常见的病原体。 SCAP是一种严重且危及生命的感染，治疗方案的核心必须是有效覆盖所有可能的致病菌。许多国家制定了SCAP的诊断和治疗指南，不同的指南有不同的患者分层标准和治疗药物，但总的原则是相同的，即：覆盖解释患者病变特征和当地流行致病菌以及抗生素耐药性的最可能的所有致病菌。病例分享 55 岁男性，既往体健，因发热咳嗽 3 天入院。患者 3 天前发热，热峰 40 ℃，伴干咳、胸闷、乏力与反应迟钝、小便失禁。查体：体温 36.0 ℃，血压 105/56 mmHg，R 35 次/分，指脉氧 92%（面罩无创通气中，氧浓度 60%），嗜睡，呼之能应，两肺湿罗音，心率 90 次/分，律齐，无杂音，下肢无浮肿。实验室检查：血常规：WBC 4.05 × 109/L，N% 85.4%，淋巴细胞计数 0.38 ×109/L，CRP > 220 mg/L，PCT 14.99 ng/mL 。血生化：AST 283 U/L，ALT 91 U/L，LDH > 2150 U/L，BUN 15 mmol/L ，Cr 295 μmol/L，Na+132.7 mmol/L。血气分析：PH 7.37，PaO266 mmHg（FiO2 60%），PaCO256 mmHg；新冠核酸检测（-）、流感检测（-）。胸部 CT：提示左肺上叶与右肺中叶炎症。诊断：重症社区获得性肺炎、呼吸衰竭。后因氧合持续恶化，急诊气管插管机械通气后收入呼吸科。当时的值班医生分析，重症社区获得性肺炎（SCAP）病情危重，死亡率较高。使用碳青霉烯类药物联合万古霉素/利奈唑胺，覆盖广谱耐药革兰氏阴性菌和耐药革兰氏阳性菌（包括MRSA），大包围合情合理，因此选择亚胺培南/西司他丁联合万古霉素经验性抗菌治疗。问以上方案是否合理？不合理！答《中国成人社区获得性肺炎诊断和治疗指南（2016年版）》推荐（1）对于无基础疾病的青壮年重症CAP患者，推荐使用青霉素类/酶抑制剂复合物（阿莫西林/克拉维酸、氨苄西林/舒巴坦、阿莫西林/舒巴坦等）、第三代头孢菌素（静脉注射：头孢曲松、头孢唑肟、头孢噻肟等；口服：头孢地尼、头孢泊肟酯、头孢克肟等）、头霉素类（头孢西丁、头孢替尼、头孢美唑、头孢米诺等）、氧头孢烯类（拉氧头孢、氟氧头孢）、厄他培南等碳青霉烯类联合大环内酯类或单用呼吸喹诺酮类静脉治疗。（2）对于老年或有基础疾病的重症CAP患者，推荐青霉素类/酶抑制剂复合物、第三代头孢菌素或其酶抑制剂复合物、厄他培南等碳青霉烯类联合大环内酯类，或联合呼吸喹诺酮类。（3）对于年龄≥65岁或有基础疾病的住院CAP患者，应考虑肠杆菌科细菌感染的可能。进一步评估产ESBL（超广谱β-内酰胺酶）菌感染的风险。高危患者的经验性治疗包括头霉素类、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦或厄他培南等。（4）对于具有铜绿假单胞菌感染危险因素的CAP，推荐使用具有抗假单胞菌活性的β-内酰胺类药物(头孢他啶、头孢吡肟、哌拉西林、氨曲南、哌拉西林/他唑林)、替卡西林/克拉维酸、头孢哌酮/舒巴坦、亚胺培南/西司他丁、头孢哌酮、美罗培南等），具有抗假单胞菌活性喹诺酮类（环丙沙星、左氧氟沙星），具有抗假单胞菌活性的β-内酰胺类联合喹诺酮类或氨基糖苷类（阿米卡星、庆大霉素等），具有抗假单胞菌活性活性β-内酰胺类、氨基糖苷类、喹诺酮类三药联合。该患者为青壮年，无基础疾病，指南没有推荐使用亚胺培南/西司他丁，也没有推荐万古霉素、利奈唑胺等抗MRSA药物。该患者入院后最初接受经验性亚胺培南/西司他丁联合万古霉素抗菌治疗，但高热持续，氧合状况未见改善。第5天，肺泡灌洗液报告检出嗜肺军团菌，病原学诊断：军团菌肺炎，故患者改用阿奇霉素抗菌治疗。患者病情好转，体温逐渐恢复正常，最终顺利拔管出院。《2019 ATS/IDSA临床实践指南：成人社区获得性肺炎的诊断和治疗》推荐（1）对于无耐甲氧西林金黄色葡萄球菌（MRSA）或铜绿假单胞菌感染风险的重症CAP患者，推荐使用β-内酰胺类药物（氨苄西林/舒巴坦、头孢曲松、头孢噻肟、头孢洛林）联合口服大环内酯类药物（阿奇霉素、克拉霉素）或呼吸道喹诺酮类药物（左氧氟沙星、吉米沙星、莫西沙星）。（2）有MRSA或铜绿假单胞菌危险因素的成人CAP患者应选择抗MRSA药物（万古霉素、利奈唑胺）、抗铜绿假单胞菌药物（哌拉西林/他唑巴坦、头孢他啶、头孢吡肟、亚胺培南、氨曲南、美罗培南）。目前，我国市场上销售的碳青霉烯类抗生素有5个品种：亚胺培南、帕尼培南、比阿培南、美罗培南和厄他培南。碳青霉烯类抗菌药物抗菌谱广，抗菌活性强，对需氧菌和厌氧菌均具有抗菌作用，特别是多重耐药革兰氏阴性杆菌，如产ESBL肠杆菌科细菌有很强的抗菌活性。近年来，我国碳青霉烯类抗菌药物临床应用中出现了一些不合理的现象，耐青霉烯耐药革兰阴性杆菌感染的发病率呈快速上升趋势，尤其是碳青霉烯耐药肺炎克雷伯菌、碳青霉烯耐药鲍曼不动杆菌、碳青霉烯耐药大肠埃希菌和碳青霉烯耐药铜绿假单胞菌等因其高耐药性和快速传播能力，给临床诊疗和感染防控带来巨大挑战。《抗菌药物临床应用指导原则（2015年版）》中明确了碳青霉烯类抗菌药物临床应用的适应证具有多重耐药性但对此类药物敏感的需氧革兰氏阴性杆菌引起的严重感染，包括肺炎克雷伯菌、阴沟肠杆菌、大肠埃希菌、柠檬酸杆菌、铜绿假单胞菌、粘质沙雷菌等肠杆菌科细菌、不动杆菌属等细菌所致血流感染、下呼吸道感染等。 2021年，BMJ发表的综述《Management of pneumonia in critically ill patients》表明，与非大环内酯类药物相比，β-内酰胺类药物联合大环内酯类药物可显著改善重症CAP患者预后。与氟喹诺酮类药物相比，β-内酰胺类药物联合大环内酯类药物治疗可降低重症肺炎患者的14天和30天死亡率。联合治疗的优点是覆盖非典型病原体，并可能受益于大环内酯类药物的免疫调节作用，以减轻细菌毒力因子和过度的全身炎症反应。 CAP的经验性抗感染治疗必须以临床微生物思维为基础，避免抗菌药物的过度使用，并及时考虑特殊病原体感染或非感染性肺部疾病。综上所述，对于重症CAP患者，初始治疗为大环内酯类或氟喹诺酮类药物与β-内酰胺类药物联合治疗。β-内酰胺的选择基于假单胞菌风险因素的存在，对于MRSA的额外覆盖基于特定风险因素的存在决定。根据 IDSA/ATS 指南的建议，只有在患者存在MRSA危险因素（既往MRSA呼吸道隔离、过去90天内住院和过去90天内使用非肠道抗生素，以及当地确认的MRSA的危险因素）时，才针对MRSA进行抗菌治疗，使用药物如万古霉素或利奈唑胺。参考文献： [1]瞿介明,曹彬.中国成人社区获得性肺炎诊断和治疗指南(2016年版)[J].中华结核和呼吸杂志,2016,39(04):253-279. [2]郑旭婷,陈佰义.社区获得性肺炎经验性抗感染治疗的临床微生物思维[J].中华结核和呼吸杂志,2021,44(06):588-591. [3]中华人民共和国国家卫生健康委员会.抗菌药物临床应用指导原则（2015 年版）[J].chrome-extension://ibllepbpahcoppkjjllbabhnigcbffpi/http://www.nhc.gov.cn/ewebeditor/uploadfile/2015/09/20150928170007470.pdf. [4]中华人民共和国国家卫生健康委员会.碳青霉烯类抗菌药物临床应用专家共识[J]. http://www.nhc.gov.cn/cms-search/xxgk/getManuscriptXxgk.htm?id=95f65ca473b44746b24590e94468b8ff. [5]郑旭婷,陈佰义.社区获得性肺炎经验性抗感染治疗的临床微生物思维[J].中华结核和呼吸杂志,2021,44(06):588-591. [6]黄丹,徐中良.2016—2020年医院碳青霉烯类抗菌药物与常见碳青霉烯耐药革兰阴性杆菌调查分析[J].临床合理用药杂志,2022,15(14):40-43.DOI:10.15887/j.cnki.13-1389/r.2022.14.012. [7]C Cillóniz, Torres A , Niederman M S . Management of pneumonia in critically ill patients[J]. BMJ (Clinical research ed.), 375:e065871. 编辑：Yan

微生物疗法

2024-04-07

·佰傲谷BioValley

IL-2/IL-2R研究简史

1976年发现的IL-2，在整个免疫治疗史上，有着不可替代的位置。Rosenberg称之为第一个人类肿瘤有效的免疫治疗方法。IL-2/IL-2R受体里程碑研究 1976年 NCI肿瘤细胞生物学实验室的RobertGallo，使用PHA刺激淋巴细胞产生条件培养基培养骨髓细胞，其中90%的T细胞长达9个月的生存维持。在此之前，原代T细胞无法体外培养，是免疫学发展的巨大瓶颈性技术问题。这个未被纯化的成分称之为T细胞生长因子（TCGF）。条件培养基培养骨髓细胞（文献1）1980年NCI肿瘤细胞生物学实验室的RobertGallo，通过离子交换色谱和凝胶分离，从条件培养基中分离浓缩了TCGF，并且得出了大致的分子量约15KD。纯化IL-2电泳（文献2）1983年日本癌症研究基金会肿瘤研究中心，Junji Hamuro等人，克隆了IL-2的基因，完成了测序工作。人们可以完整的了解这个T细胞生长因子的基因和氨基酸序列等基础信息。但是为什么第一个被克隆的细胞因子成为IL-2而不是IL-1呢？原因是，当初有科学家认为，有另外一个细胞因子刺激了IL-2的产生，那个未知的因子应该是1。IL-2序列（文献3）IL-2受体的发现和克隆 1984年Nature发表了三篇IL-2受体α克隆的文章（文献4，5，6），分别来自于Immunex 公司（2002年Amgen收购），NCI，和日本京都大学。 1986年NIH国立儿童健康与人类发育研究所在Science发表文章（文献7），发现了IL-2另外一个受体p70，1986和1987年还有多篇文章报道IL-2 p70受体。1990年日本东北大学医学院，1991京都大学分别发表文章发现IL-2Rγ（文献8，9）。至此，IL-2受体α，β，γ被发现。之后IL-2和受体的结合，被Stanford的科学家解析。IL-2-IL-2Rα，β，γ复合物结构（文献10）IL-2/IL-2R药物开发重组IL-21983年IL-2基因被克隆，是IL-2药物开发的里程碑式基础研究，1983年和1984年多个实验室进行了IL-2的大肠杆菌表达。 IL-2临床试验统计（文献16）1984年11月，一个33岁黑色素瘤转移的病人接受重组IL-2治疗，肿瘤消退，此后病人无疾病生存29年。1985年Rosenberg在肝癌转移小鼠模型注射重组IL-2，获得很好的治疗效果（文献11）。1985年Rosenberg等在新英格兰医学杂志报道，使用IL-2和LAK细胞进行了25个癌症转移病人的临床研究。Rosenberg 2014年发文评述IL-2是第一个人类肿瘤有效的免疫治疗方法（文献13）。 1991年诺华与linigen联合研发的重组IL-2药物 Proleukin（Aldesleukin，阿地白介素）被FDA批准治疗转移性肾癌，1998年批准治疗转移性黑色素瘤。但是因为半衰期短，治疗窗口窄，毒副作用大，且同时刺激Treg活化，限制了临床使用。新型IL-2开发（PEG化，偏向性IL-2） IL-2R有α（CD25），β（CD122），γ（CD132），其中，α为低亲和力受体，且下游无信号传导，β和γ组成中等亲和力的受体，下游可以通过JAK传导信号，在α参与的情况下，亲和力增强为高亲和力受体。IL-2受体（文献17）从1990s开始，很多的科研单位和企业开始，通过突变改变IL-2和不同受体亚单位亲和力，以增加活力，降低毒性。2000年Bayer 设计了BAY50-4798，选择性结合IL-2Raβγ，减少和IL-2βγ的结合，减少IL-2Rβγ+ NK细胞介导的毒性。但是最终临床治疗和传统IL-2比较，没有改善。BAY50-4798结构及作用（文献14）NKTR-214NKTR-214是由美国Nektar公司开发的一种针对CD122 (IL-2Rβ)抗原的偏向型激动剂,其通过靶向作用于CD8+效应T细胞以刺激肿瘤杀伤T细胞的增殖,从而利用患者自身免疫系统对抗癌症。NKTR-214通过对首个肿瘤免疫药物aldesleukin进行聚乙二醇(PEG)修饰,有效克服了其严重的毒副作用并延长起效时间。THOR-707Synthorx公司（赛诺菲25亿美金收购）产品，通过向宿主细胞转入非天然氨基酸，在该位点实现定点PEG偶联，和IL-2Rα低亲和力，但是和IL-2Rβγ有接近天然的亲和力，选择性激活CD8+T细胞，不激活Treg。NCT04009681，A Study Evaluating Safety and TherapeuticActivity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors(THOR-707-101)，Phase1/2SHR-1916 12月25日恒瑞偏向性IL-2，SHR-1916获批临床。SHR-1916是恒瑞医药自主研发的全新PEG修饰和位点突变的IL-2分子，可以通过激活JAK1/JAK3/STAT5信号通路，促进CD8⁺T和NK细胞增殖，发挥抗肿瘤作用。Immunocytokine（抗体-IL2偶联）通过靶向肿瘤抗原抗体将IL-2携带至肿瘤局部，是另外一种策略，可以增加半衰期，增强靶向性，降低毒性。hu14.18-IL2hu14.18-IL2（EMD273063），由EMD Serono研发，是一种抗GD2免疫因子，由抗GD2抗体14.18（抗体）和两分子的IL-2（免疫因子）融合而成的蛋白，主要用于治疗黑色素瘤。临床研究：NCT00590824，Pilothu14.18-IL2 in Resectable Recurrent Stage III or Stage IV Melanoma，phase2 在一些高复发风险的黑色素瘤患者中，使用IC治疗的患者出现了长时间的无瘤生存。 L19-IL2Philogen S.p.A.公司研发，L19靶向细胞外基质（ECM）纤维连接蛋白异构体B-FN的的结构域B（ED-B）。NCT02957019，A PhaseI/II Study of the Tumor-targeting Human L19-IL2 Monoclonal Antibody-cytokineFusion Protein in Combination With Rituximab in Relapsed or Refractory DiffuseLarge B-cell Lymphoma (DLBCL)NCT04362722，IntratumoralAdministration of Daromun in Non-melanoma Skin Cancer Patients (DUNCAN)，phase2Philogen S.p.A.还开发了F16IL2，有多个临床在开展，但是进度未更新。RO6874281RO6874281，来自于Roche，是IL-2突变体与靶向FAP的单抗融合而成的双特异性蛋白，其中靶向肿瘤胶质抗原FAP的单抗用于将蛋白相对准确地定位到肿瘤部位，IL-2突变体部分则偏向性地结合和调控肿瘤微环境中的T细胞表面的IL-2Rβγ二聚体，从而激活微环境中的抗肿瘤免疫效果。 NCT03875079（Metastatic Melanoma），NCT03063762（Metastatic Renal Cell Carcinoma），NCT02627274（联用Trastuzumab or Cetuximab），NCT03386721（实体瘤，联用Atezolizumab），NCT03193190（PDAC）IL-2R抗体阻断性抗体用于炎症性疾病，非阻断性抗体用于肿瘤免疫治疗。阻断性抗体Zinbryta(daclizumab)AbbVie，Inc.和Biogen适用为有多发性硬化症(MS)的复发型成年患者的治疗白介素-2受体阻断抗体7例严重不良反应，主要为脑炎和脑膜炎，这才紧急启动撤市程序。 IL-2R alpha嵌合体抗体Basiliximab/巴利昔单抗/舒莱Novartis预防首次肾移植术后的急性器官排斥国内注册号：S20171040非阻断性抗体RG6292非阻断性CD25抗体，选择性清除Treg。详细内容可阅读：Roche 新型CD25抗体选择性清除调节性T细胞，增强抗肿瘤免疫参考文献Morgan DA, Ruscetti FW, GalloRC: Selective in vitro growth of T lymphocytes from normal human bone marrows.Science 1976, 193: 1007e1008J.W. Mier, R.C. Gallo,Purification and some characteristics of human T-cell growth factor fromphytohemagglutinin-stimulated lymphocyte-conditioned media, Proc.Natl. Acad.Sci. USA (1980)aniguchi T,et al: Structure andexpression of a cloned cDNA for human interleukin-2. Nature 1983, 302:305e310Cosman, D.et al, (1984).Cloning, sequence and expression of human interleukin-2 receptor. Nature 312,768–771.Leonard, W.J.,etal.(1984).Molecular cloning and expression of cDNAs for the human interleukin-2 receptor.Nature 311, 626–631.Nikaido, T., et al (1984).Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature 311,631–635.Sharon, M., et al. (1986).Novel interleukin-2 receptor subunit detected by cross-linking underhigh-affinity conditions. Science 234, 859–863.Takeshita, T., et al. (1990).An associated molecule, p64, with high-affinity interleukin 2 receptor. Int.Immunol. 2, 477–480.Saito, Y.,et al. (1991).Biochemical evidence for a third chain of the interleukin-2 receptor. J. Biol.Chem. 266, 22186–22191.X. Wang, M. Rickert, K.C.Garcia, Structure of the quaternary complex of interleukin-2 with Its α, ß, andγc Receptors. Science (80-) 310 (2005) 1159 LP–1163Lafreniere R, Rosenberg SA.1985. Successful immunotherapy of murine experimental hepatic metastases withlymphokine activated killer cells and recombinant interleukin 2. Cancer Res45(8):3735–3741.Rosenberg SA, et al. 1985.Observations on the systemic administration of autologous lymphokine-activatedkiller cells and recombinant interleukin-2 to patients with metastatic cancer.N Engl J Med 313(23):1485–1492.Rosenberg SA. 2014. IL-2: thefirst effective immunotherapy for human cancer. J Immunol 192(12):5451–5458.Shanafelt AB, et al. 2000. AT-cell-selective interleukin 2 mutein exhibits potent antitumor activity and iswell tolerated in vivo. Nat Biotechnol 18(11):1197–1202.Carnemolla B, Borsi L, Balza Eet al (2002) Enhancement of the antitumor properties of interleukin-2 byits targeted delivery to the tumor blood vessel extracellular matrix. Blood99(5):1659– 1665Alexy Orozco Valencia，et al，Interleukin-2 as immunotherapeutic in the autoimmune diseases，International Immunopharmacology 81 (2020) 1062962Rosanne Spolski，et al，Biology and regulation of IL-2: from molecular mechanisms to human therapy，Nat Rev Immunol . 2018 Oct;18(10):648-659.本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处···

免疫疗法并购细胞疗法

2024-03-07

·BioSpace

Vast Therapeutics Expands Leadership Team with Appointment of Dr. Paul Bruinenberg as Chief Medical Officer

Addition of CMO, Medical Director Chris Polage, MD, and enhancements in clinical operations position Company for success in the clinical development of ALX1 in bronchiectasis MORRISVILLE, N.C., March 7, 2024 /PRNewswire/ -- Vast Therapeutics today announced the addition of Paul Bruinenberg, MD, MBA as Chief Medical Officer. Dr. Bruinenberg brings over 30 years of experience as a clinical development executive in respiratory medicine and orphan diseases. This appointment and the recent addition of microbiologist and clinical diagnostics expert Chris Polage, MD, as Medical Director, significantly bolster the company's clinical development expertise in pulmonary infectious diseases and medical microbiology. "Paul's development experience will guide Vast Therapeutics as we successfully transition to a clinical-stage organization," said Nate Stasko, Chief Executive Officer at Vast Therapeutics. "He's been here before. His early-stage clinical experience in cystic fibrosis and non-cystic fibrosis bronchiectasis patient populations is a perfect match for our drug candidates that we believe will reshape the respiratory infectious disease landscape." "It is an amazing opportunity to join a company with an accepted IND for a novel treatment modality that shows promising efficacy against chronic infections caused by Pseudomonas aeruginosa and non-tuberculosis mycobacteria," commented Paul Bruinenberg, Chief Medical Officer at Vast Therapeutics. "The high unmet medical need in this therapeutic area is significant. I am excited to advance our nebulized therapy to maximize clinical outcomes for these patients without concerns of renal toxicity and emergence of antibiotic resistance." Vast plans to initiate its Phase 1 clinical development program in Q2 2024 and one or more proof-of-concept studies in subjects with bronchiectasis in 2025. Paul Bruinenberg, MD, MBA – Chief Medical Officer Dr. Bruinenberg has over 30 years' experience in the pharmaceutical and biotechnology industry. He brings a wealth of respiratory infectious disease experience researching rare diseases like cystic fibrosis (CF), non-CF bronchiectasis (NCFB), tuberculosis (TB) and non-tuberculosis mycobacteria (NTM). His career includes development of several inhaled therapies including the approval of Pulmozyme® as the first mucolytic for CF as well as the early development of inhaled liposomal ciprofloxacin for the treatment of chronic Pseudomonas aeruginosa infections. Most recently, Dr. Bruinenberg served as the Senior Medical Officer of the TB Alliance leading clinical development against mycobacterial infections. Previously, he held medical leadership roles at Eagle Pharmaceuticals, Aradigm Corporation, Astellas and Roche, having a key role in the development and approval of 12 new drugs (Pulmozyme®, Pretonamid®, Globocef®, Rocephin®, Quinodis® Bosentan®, Xolair®, CellCept®, Zenapax®, Belrapzo®, Bendeka®, and Ryanodex®). Dr. Bruinenberg is a graduate of the medical school of the University of the Stellenbosch, South Africa and obtained two MBAs from the University of Nijenrode in the Netherlands and Rochester University in the USA. Chris Polage, MD – Medical Director Dr. Polage is a physician-scientist and board-certified medical microbiologist with NIH clinical research training and over 15 years of experience leading top academic clinical laboratories. His award-winning research and publications have been cited more than 2500 times in the medical and scientific literature and changed medical practice regarding the diagnosis and treatment of C. difficile, an urgent antimicrobial resistance threat. Before coming to Vast, he was Medical Director of the Duke University Clinical Microbiology Laboratory where he oversaw specialized testing for a broad array of patient populations including CF and NCFB patients. Dr. Polage is a diagnostics expert for the NIAID/NIH Antimicrobial Resistance Leadership Group and an adjunct Associate Professor of Pathology at Duke University. He received his Doctor of Medicine from the University of New Mexico with residency and fellowship training at the University of Colorado and University of Utah/ARUP Laboratories, including two years of medical microbiology with a special focus on mycobacterial testing. About Vast Therapeutics Vast is a life science company focused on breaking the debilitating cycle of infection and chronic inflammation in respiratory diseases. This cycle affects patients across the entire spectrum of human life, ranging from children with rare orphan diseases like Cystic Fibrosis to adults with highly prevalent diseases like chronic obstructive pulmonary disease (COPD). We believe our product candidates may provide an effective treatment for patients infected with Pseudomonas aeruginosa, NTM, and other drug-resistant microbes. Contact: Nathan Stasko Chief Executive Officer Vast Therapeutics, Inc. nstasko@vasttherapeutics.com

高管变更微生物疗法

100 项与达克珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03639	达克珠单抗	L04AC01	DB00111

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
多发性硬化症	美国	Biogen, Inc.	2016-05-27
肾移植排斥反应	欧盟	Roche Registration Ltd.	1999-02-26
肾移植排斥反应	冰岛	Roche Registration Ltd.	1999-02-26
肾移植排斥反应	列支敦士登	Roche Registration Ltd.	1999-02-26
肾移植排斥反应	挪威	Roche Registration Ltd.	1999-02-26
器官移植排斥	美国	F. Hoffmann-La Roche Ltd.	1997-12-10

未上市

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适应症	最高研发状态	国家/地区	公司	日期
同种异体移植排斥反应	临床2期	美国	Roche Pharma AG	2003-10-01
心脏移植排斥反应	临床2期	美国	Roche Pharma AG	2003-10-01
溃疡性结肠炎	临床2期	美国	Abbott Biotherapeutics Corp.	2003-04-01
溃疡性结肠炎	临床2期	比利时	Abbott Biotherapeutics Corp.	2003-04-01
溃疡性结肠炎	临床2期	加拿大	Abbott Biotherapeutics Corp.	2003-04-01
哮喘	临床2期	美国	Abbott Biotherapeutics Corp.	2001-09-01
持续性哮喘	临床2期	美国	Abbott Biotherapeutics Corp.	2001-09-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01797965 (EXTEND, Pubmed \| Ther Adv Neurol Disord) 人工标引	临床3期	复发性多发性硬化	1,203	daclizumab beta	繭製淵選糧衊繭網網構(襯醖鹽鹹襯繭餘襯繭醖) = 網製廠顧願獵窪願遞顧鏇艱膚醖淵簾淵糧鬱遞 (積壓顧遞廠襯範鬱鹽選 ) 更多	不佳	2021-02-26
NCT01051349 (SELECTED, Pubmed) 人工标引	临床2期	复发-缓解型多发性硬化	455	Daclizumab	衊選顧夢窪繭蓋網鑰構(繭鬱齋製鏇顧夢獵鹹製) = 餘繭鬱鹽淵膚鬱鏇簾憲憲鬱夢齋憲鬱襯壓鏇膚 (鹹鑰觸衊簾糧糧膚鏇艱 ) 更多	积极	2020-10-01
NCT01797965 (EXTEND, CTgov)	临床3期	复发-缓解型多发性硬化	1,501	IFN β-1a+DAC HYP (IFN β-1a 30 µg (301)/DAC HYP 150 mg (303))	網選窪選蓋積遞窪壓顧(齋糧襯膚醖選壓壓積憲) = 鹽襯夢獵願製餘簾觸醖觸觸網遞築觸夢遞蓋願 (夢窪壓艱夢獵鹽繭遞鹽, 窪觸廠淵鹽鑰顧鹽壓襯 ~ 餘壓衊獵獵鹹憲淵遞簾) 更多	-	2019-12-04
NCT01797965 (EXTEND, CTgov)	临床3期	复发-缓解型多发性硬化	1,501	DAC HYP (DAC HYP 150 mg (301) /DAC HYP 150 mg (303))	網選窪選蓋積遞窪壓顧(齋糧襯膚醖選壓壓積憲) = 製積憲鹽醖製遞製構鑰觸觸網遞築觸夢遞蓋願 (夢窪壓艱夢獵鹽繭遞鹽, 齋鹽糧鹹遞蓋繭積繭鹽 ~ 醖鹹糧積窪築顧窪餘糧) 更多	-	2019-12-04
NCT02881567 (SUSTAIN, CTgov)	临床3期	复发-缓解型多发性硬化	41	Daclizumab	艱醖襯顧獵願壓糧鏇鑰(繭鏇膚製網繭築選艱齋) = 窪鬱築廠膚網齋襯鬱廠膚齋鹽鏇艱鹹壓網衊鏇 (鏇顧構網艱廠夢製艱鬱, 積醖膚網淵廠簾獵艱壓 ~ 簾糧壓鏇憲繭壓簾鹽襯) 更多	-	2019-09-24
NCT01064401 (DECIDE, Pubmed) 人工标引	临床3期	多发性硬化症	24	daclizumab beta	膚艱蓋範顧衊鹽構齋範(範憲築願衊鏇夢遞齋鏇): HR = 0.73 (95% CI, 0.55 ~ 0.98) 更多	相似	2018-12-01
NCT01064401 (DECIDE, Pubmed) 人工标引	临床3期	多发性硬化症	24	interferon beta-1a	膚艱蓋範顧衊鹽構齋範(範憲築願衊鏇夢遞齋鏇): HR = 0.73 (95% CI, 0.55 ~ 0.98) 更多	相似	2018-12-01
NCT01051349 (SELECTED, CTgov)	临床2期	复发-缓解型多发性硬化	410	trivalent seasonal influenza vaccine+BIIB019 (Daclizumab)	鏇壓鏇願廠窪鏇鏇齋鹽(鹽積衊觸鏇簾壓廠築艱) = 窪繭齋鏇構膚淵糧繭顧選簾網積網窪襯鹽鹽齋 (積製構廠鑰衊醖蓋壓膚, 範簾範積淵艱積憲鑰範 ~ 壓夢鹹範簾壓鏇遞積範) 更多	-	2018-11-09
ECTRIMS2018	N/A	脑炎 \| 脑膜脑炎	-	Daclizumab	簾糧餘構淵淵窪遞鹹選(範艱鹽襯繭襯衊夢顧醖) = 7 patients who developed meningitis/meningoencephalitis after undergoing daclizumab therapy 觸鏇憲衊顧獵築膚積鏇 (淵壓積製選憲製遞廠窪 ) 更多	-	2018-10-09
NCT01064401 (DECIDE, Pubmed) 人工标引	临床3期	复发-缓解型多发性硬化	1,841	daclizumab beta	醖鹹鏇獵淵鏇觸夢積遞(築觸廠憲憲願壓憲夢觸): P-Value = 0.0274	积极	2018-05-01
NCT01064401 (DECIDE, Pubmed) 人工标引	临床3期	复发-缓解型多发性硬化	1,841	IM IFN beta-1a	醖鹹鏇獵淵鏇觸夢積遞(築觸廠憲憲願壓憲夢觸): P-Value = 0.0274	积极	2018-05-01
NCT01051349 (SELECTED, AAN2018)	临床2期	-	455	Daclizumab beta 150mg	窪繭製觸選範餘餘網壓(鏇觸蓋鹽糧夢鬱鏇簾獵) = 築鹽鹹獵壓鹽築襯鏇艱築鬱顧鹹網廠膚襯齋夢 (獵糧選鏇窪餘網鏇願積 )	-	2018-04-10
ZEUS Study (AAN2018)	N/A	-	522	Daclizumab beta	壓網衊淵糧夢獵糧鬱衊(窪繭糧製糧繭醖遞齋網) = 觸廠構觸餘齋艱鏇鹽選鏇鑰蓋鑰蓋壓艱鬱積醖 (鑰淵簾衊淵淵襯築淵範 ) 更多	积极	2018-04-10