更新于：2024-04-01

IL-6RA

白细胞介素-6受体α亚基

更新于：2024-04-01

基本信息

别名

白细胞介素-6受体α亚单位、CD126、gp80

+ [15]

简介

Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells (By similarity). Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364). In complex with IL6, is required for induction of VEGF production (PubMed:12794819). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity). Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364). In complex with IL6, is required for induction of VEGF production (PubMed:12794819). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity). Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis (PubMed:30995492, PubMed:31235509). The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable).

关联

项与 IL-6RA 相关的药物

Tocilizumab biosimilar(Fresenius Kabi )

托珠单抗生物类似药(Fresenius Kabi )

靶点

IL-6RA

作用机制

IL-6RA拮抗剂

在研机构

Fresenius Kabi Deutschland GmbH [+1]

原研机构

Fresenius Kabi Deutschland GmbH

在研适应症

新型冠状病毒感染 [+6]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2023-09-15

Tocilizumab biosimilar (Livzon)

托珠单抗生物类似药（丽珠）

靶点

IL-6RA

作用机制

IL-6RA拮抗剂

在研机构

珠海市丽珠单抗生物技术有限公司

原研机构

珠海市丽珠单抗生物技术有限公司

在研适应症

类风湿关节炎

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2023-01-18

Tocilizumab-bavi

托珠单抗生物类似药 (百奥泰生物)

靶点

IL-6RA

作用机制

IL-6RA拮抗剂

在研机构

Biogen MA, Inc. [+1]

原研机构

百奥泰生物制药股份有限公司

在研适应症

多关节型幼年特发性关节炎 [+4]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2023-01-16

790

项与 IL-6RA 相关的临床试验

NCT03787290 / Suspended临床2期

Examining Immune-Based Mechanisms of Action for Mild-Intensity Whole Body Hyperthermia (WBH) in the Treatment of Major Depressive Disorder

Overall, the objective of this pilot study is to utilize the IL-6 receptor antagonist tocilizumab to prospectively evaluate the role of IL-6 in the antidepressant and immunological effects of whole body hyperthermia (WBH). The study seeks to replicate findings thus far that WBH has an antidepressant effect by administering the intervention at a site not involved in studies to date. Moreover, the current proposal may help the investigators better understand the role of IL-6 in the pathogenesis and treatment of depression which might point to novel immune-based interventions for Major Depressive Disorder (MDD). Finally, the current proposal holds promise for better understanding of a novel treatment for MDD, which is among the leading causes of health-related disability in the world.

开始日期2025-12-01

申办/合作机构

The General Hospital Corp.

[+1]

NCT06016517 / Not yet recruitingN/AIIT

Application of the N-of-1 Trial Design in Rheumatoid Arthritis

The goal of this N-of-1 study is to learn about treatment for individual patients who have rheumatoid arthritis (RA,) for which many treatments are available. The treatments are different in how they work, the way they are given, side- effects, and cost. While treatment guidelines are available, finding the best treatment order of treatments is often based on physician choice. The main question this study aims to answer are:
What are the effects of different treatments on RA symptoms and condition for each individual patient
What is the effectiveness of different treatments across all patients enrolled in the N-of-1 study
Participants will be enrolled and randomized to a sequence of three U.S. Food and Drug Administration (FDA) approved RA medications: 1. adalimumab, 2. sarilumab, and 3. upadacitinib. Participants will be asked to complete questionnaires about their condition and quality of life weekly (either in clinic or remotely) and report their level of pain daily (remotely).

开始日期2024-05-15

申办/合作机构

Tufts Medical Center, Inc.

NCT06037460 / Not yet recruiting临床3期IIT

TocilizuMab discontinuAtion in GIant Cell Arteritis

Giant cell arteritis (GCA) is a large-vessel vasculitis that typically occurs in people over the age of 50.
Corticosteroids (GC) are the cornerstone of treatment for GCA. French guidelines recommend starting at 0.7 or 1 mg/kg/day at diagnosis, depending on the occurence of ischemic complication(s). Then, it is recommended to gradually decrease their dose to achieve withdrawal in 12 to 24 months.
Despite this treatment, 47% of patients relapse. Relapses are favored by rapid reduction of corticosteroid doses and large vessel involvement at diagnosis. Fortunately, relapses are severe in only 3.3% of cases and ischemic complications are very rare. However, this contributes to prolonging the duration of corticosteroid treatment and thus the risk of cortico-induced adverse events, which have not been significantly reduced in the last 20 years. The main risk factors for the development of steroid-related complications are advanced age and cumulative steroid dose.
For this reason, the development of cortisone-sparing strategies is necessary to improve the management of patients with GCA. Thanks to major advances in the understanding of the pathophysiological mechanisms of GCA, new therapeutic targets have been discovered. For example, the efficacy of tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, has been demonstrated in two phase 2 trials and one phase 3 trial, leading to its approval for the management of patients requiring rapid reduction in corticosteroid doses and/or those relapsing repeatedly on prednisone >7.5 mg/day. In recently published US guidelines, TCZ can even be used at diagnosis to reduce the need for corticosteroid therapy.5 Indeed, TCZ appears to be remarkably effective in controlling GCA activity and saves approximately 2000 mg of prednisone in cumulative dose.
At present, the place of TCZ compared to methotrexate in the therapeutic strategy is still being evaluated, notably through the METOGiA study (PHRC-N 2017), which is being conducted by our team. Inclusions for METOGiA ended in March 2023 with results expected in 2025. Outside of this study, approximately 1500 patients are currently receiving TCZ treatment for GCA (data from ROCHE-CHUGAI).
There is no doubt that TCZ treatment is effective and rather well tolerated in the elderly population, but it generates problems that are not solved to date:
the cost (
900€/month)
the difficulty monitoring these patients because the biological markers usually used to monitor GCA (CRP, ESR, fibrinogen) can no longer be measured since TCZ blocks their production by the hepatocytes. Monitoring of disease activity therefore requires very careful clinical examination and the use of expensive imaging tests such as PET scans because GCA can be active despite normal ESR, CRP and fibrinogen levels. Some studies suggest that monitoring serum IL-6 may help identify patients with active disease, but this test is not readily available and the threshold above which relapse should be suspected is unclear because TCZ induces an increase in serum IL-6 levels by blocking IL-6 receptors, even in patients in remission.
For the same reasons, infections are difficult to detect in patients treated with TCZ.
This raises the question of how to discontinue this treatment, especially since other treatments that do not interfere with CRP, ESR, or fibrinogen measurements are being evaluated.
This shows that this treatment tends to be prolonged well beyond one year when the disease is often in remission without corticosteroids. This is probably related to two factors: 1/ the fear of relapse after treatment withdrawal; 2/ the absence of a scheme for withdrawing TCZ.
The risk of relapse after stopping TCZ has been reported in several studies, in particular the long-term follow-up of phase 2 and 3 trials that demonstrated the efficacy of TCZ for the treatment of GCA. Overall, regardless of the duration of TCZ treatment, the risk of relapse is approximately 40% 6 months after the last injection of TCZ, and the risk of relapse is higher if the large arteries (aorta and its branches) are involved.
Thus, although the available data are limited, it appears that tapering rather than immediately stopping TCZ limits the risk of relapse after full withdrawal.

开始日期2024-04-01

申办/合作机构

Centre Hospitalier Universitaire de Dijon

100 项与 IL-6RA 相关的临床结果

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100 项与 IL-6RA 相关的转化医学

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0 项与 IL-6RA 相关的专利（医药）

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805

项与 IL-6RA 相关的文献（医药）

2024-01-19·Infectious disorders drug targets

Association of COVID with Mycosis in General.

Article

作者: Gurpreet Kaur ; Rajinder Kaur ; Sumanpreet Kaur ; Manpreet Kaur

BACKGROUND:

The COVID-19 pandemic caused by SARS-CoV-2 is a respiratory disease which created havoc worldwide, was accompanied by another peculiar, otherwise rare, secondary fungal infection Mucormycosis which was observed at exceptionally high incidence in India during the second wave of COVID-19. The article explores possible links between the two infectious diseases to understand a higher-than-normal occurrence of Mucormycosis in COVID-19 patients. Coronavirus enters the patients through ACE-2 and many other receptors like- NRP-1, TfR, CD-126, and CD-26. Virus bind to cells possessing these receptors and affect their proper functioning, disturbing homeostatic metabolism and resulting in conditions like hyperglycemia, Diabetic Ketoacidosis (DKA), low serum pH, iron overload, anemia, hypoxia, and immunosuppression as explained in the article. All these outcomes provide a very supportive environment for the attack and spread of Mucormycosis fungi. The major receptor for Mucormycosis in humans is the GRP-78. Its expression is upregulated by coronavirus entry and by hyperferritinemia, hyperglycemia, and acidic conditions prevalent in COVID patients, thus providing an easy entry for the fungal species. Upregulation of GRP-78 furthermore damages pancreatic β-cells and intensifies hyperglycemia, showing quite a synergic relationship. Inordinate rise of Mucormycosis cases in India might be explained by facts like- India possessing a large proportion of diabetic patients, emergence of a very deadly strain of coronavirus- Delta strain, higher doses of steroids and antibodies used to treat patients against this strain, overburdened health care services, sudden much higher need of oxygen supply and use of industrial oxygen could explain the Mucormycosis outbreak observed in India during the second wave of COVID-19.

OBJECTIVE:

The present review discusses the functional interdependence between COVID-19 and Mucormycosis and summarizes the possible synergic links between COVID and Mucormycosis.

CONCLUSION:

The receptors and metabolic pathways affected by COVID-19 result in severe physiological conditions- hyperglycemia, DKA, anemia, iron overload, immunosuppression, and hypoxia. All these conditions not only increase the expression of GRP-78, the major receptor for entry of fungi but also play a crucial role in providing quality media for Mucormycosis fungus to establish and grow. Hence explains the fungal epidemic observed in India during the second wave of COVID-19 in India.

2024-01-05·Acta neuropsychiatrica

Dysfunction of Circulating Endothelial Progenitor Cells in Major Depressive Disorder.

Article

作者: Ying-Jay Liou ; Mu-Hong Chen ; Ju-Wei Hsu ; Kai-Lin Huang ; Po-Hsun Huang ; Ya-Mei Bai

OBJECTIVES:

Despite mounting evidence demonstrates circulating endothelial progenitor cells (cEPCs) quantitative changes in depression, no study has investigated cEPC functions in major depressive disorder (MDD). We investigated the role of cEPC adhesive and apoptotic functions in MDD.

METHODS:

We recruited 68 patients with MDD and 56 healthy controls (HCs). The depression symptoms, anxiety, psychosomatic symptoms, subjective cognitive dysfunction, quality of life, and functional disability were evaluated using the Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression and Somatic Symptoms Scale (DSSS), Perceived Deficits Questionnaire-Depression, 12-Item Short Form Health Survey (SF-12), and Sheehan Disability Scale (SDS), respectively. Working memory and executive function were assessed using a 2-back task and Wisconsin Card Sorting Test (WCST). Inflammatory marker (soluble interleukin-6 receptor, C-reactive protein, and tumor necrosis factor-α receptor-1), cEPC adhesive and apoptotic levels were measured using in vitro assays.

RESULTS:

The MDD patients showed significantly lower cEPC adhesive levels than the HCs, and this difference in adhesive function remained statistically significant even after adjusting for inflammatory marker levels. The cEPC adhesion levels were in inverse correlations with commission and omission errors in 2-back task, the percent perseverative response and percent perseverative errors in WCST, and the DSSS and SDS scores, but in positive correlations with SF-12 physical and mental component scores. cEPC apoptotic levels did not differ significantly between the groups.

CONCLUSION:

The findings indicate that cEPC adhesive function is diminished in MDD and impacts various aspects of cognitive and psychosocial functions associated with the disorder.

2023-12-27·Pharmaceutics

Immunomodulatory Effect of Hypericin-Mediated Photodynamic Therapy on Oral Cancer Cells.

Article

作者: Marcin Olek ; Agnieszka Machorowska-Pieniążek ; Zenon P Czuba ; Grzegorz Cieślar ; Aleksandra Kawczyk-Krupka

In 2020, there were 377,713 new oral and lip cancer diagnoses and 177,757 deaths. Oral cancer is a malignancy of the head and neck region, and 90% of cases are squamous cell carcinomas (OSCCs). One of the alternative methods of treating pre-cancerous lesions and oral cancer is photodynamic therapy (PDT). In addition to the cytotoxic effect, an important mechanism of PDT action is the immunomodulatory effect. This study used the OSCC (SCC-25) cell line and the healthy gingival fibroblast (HGF-1) line. A compound of natural origin-hypericin (HY)-was used as the photosensitizer (PS). The HY concentrations of 0-1 µM were used. After two hours of incubation with PS, the cells were irradiated with light doses of 0-20 J/cm². The MTT test determined sublethal doses of PDT. Cell supernatants subjected to sublethal PDT were assessed for interleukin 6 (IL-6), soluble IL-6 receptor alpha (sIL-6Ralfa), sIL-6Rbeta, IL-8, IL-10, IL-11 IL-20, IL-32, and Pentraxin-3 using the Bio-Plex Pro^TM Assay. The phototoxic effect was observed starting with a light dose of 5 J/cm² and amplified with increasing HY concentration and a light dose. HY-PDT affected the SCC-25 cell secretion of sIL-6Rbeta, IL-20, and Pentraxin-3. HY alone increased IL-8 secretion. In the case of HGF-1, the effect of HY-PDT on the secretion of IL-8 and IL-32 was found.

项与 IL-6RA 相关的新闻（医药）

2023-07-18

·生物制品圈

造血干细胞培养涉及相关因子总结

前言近年来，干细胞在临床应用方面愈加广泛，但人体内的干细胞比例和数量极低，无法满足临床需求，所以体外扩增培养干细胞变得越来越重要，由于伦理和工艺的原因，干细胞的治疗还面临很多的问题，造血干/祖细胞及各系血细胞的表面标志较为清晰，细胞表型特征可进行定量选择，可分选，且发挥功能可相对游离，不需“生物支架”神经、血管、外科移植等复杂的“下游”工艺。因此是干细胞增殖分化的最佳模型，也便于直接用于临床。造血干细胞有高度的自我更新和多种分化潜能，可以产生所有成熟的血细胞，如红细胞、白细胞、血小板和淋巴细胞等，并且可以重建整个造血系统，造血干细胞体外扩增既要保持自我更新能力的同时还要阻止其分化，所以这是一项极具挑战性的技术。近年来大量实验表明，造血干细胞的分化依赖细胞因子，下面就为大家简单整理了一下造血干细胞培养用到的因子及其作用。● 干细胞因子（SCF）干细胞因子（stemcellfactor，SCF）是一种通过锚定并表达于所有HSC表面的酪氨酸受体c-Kit而发挥作用的因子，c-Kit表达缺陷将导致HSC扩增数量减少。目前几乎用于培养HSC实验中的所有细胞因子组合都包含SCF。另外，SCF与FL3同属于酪氨酸激酶受体TKR家族，具有扩增原始造血细胞的协同作用，通过与特异性TKR结合，向细胞内传递信号，启动早期祖细胞的分裂和增殖，使细胞走出G0期开始扩增，抑制凋亡。● 血小板生成素（TPO）TPO最初被认为是巨核细胞系特异性生长因子，属于特异性作用细胞因子,可维持巨核细胞增殖、分化、成熟、分裂及形成有功能的血小板，是扩增巨核细胞系的首选因子。近年来实验证实，在体外研究中TPO在促进HSC增殖中也起到重要的作用，并且与其他细胞因子组合使用可提高集落形成单位总数和CD34+干细胞的扩增倍数。特别是在有FL3组合中，可维持脐带血CD34+干细胞长期生长和扩增。● 白细胞介素-3白细胞介素-3（IL-3）称为肥大细胞生长因子，是一个具有多效性的细胞因子，主要由激活的T淋巴细胞产生，能够刺激多能HSC和不同谱系定向祖细胞的增殖与分化。IL-3诱导的干细胞表面受体异二聚体化后，可结合许多信号转导蛋白，如Janus激酶信号转导子与转录激活子（JAK/STAT）通路等，从而激发了一股下传的信号流，参与了干细胞的增殖调控。IL-3还可激活细胞外信号调节激酶（ERK）途径和c-jun氨基末端酶（JNK）途径，诱导干细胞的生长、增殖与存活。● 白细胞介素-6IL-6 是一种多向性细胞因子，通过调节免疫和炎症反应，在宿主防御中发挥重要作用。IL-6 由 T细胞、单核细胞、成纤维细胞、内皮细胞和角质形成细胞产生，具有多种生物学功能。它可以促进 B 细胞分化和抗体产生，协同 IL-3 在巨核细胞发育和血小板产生中发挥作用，诱导肝急性期蛋白的表达，调节骨代谢。IL-6 通过 IL-6 受体系统传递信号，IL-6 受体系统由 IL-6Rα和 gp 130 两条链组成。在胚胎干细胞中STAT3是维持胚胎干细胞不分化状态的决定性分子，而IL-6是JAK/STAT3信号通路最初的启动因子。● lFLT3配体（FL）FLT3配体是调节早期造血细胞增殖的生长因子。FLT3-配体与表达酪氨酸激酶受体FLT3的细胞结合。FLT3-配体本身并不刺激早期造血细胞的增殖，而是与其他CSFs和白细胞介素协同诱导生长和分化。与SCF不同，FLT3-配体对肥大细胞没有作用。已鉴定出FLT3-配体的多种亚型。主要的生物活性形式作为跨膜蛋白(209a.)的胞外区域锚定在细胞表面。所述膜结合异构体可被蛋白质裂解生成具有生物活性的可溶性异构体。● Fms样酪氨酸激酶3CD34+CD38dim细胞高度表达的Fms样酪氨酸激酶3（FL3），通过与其特异性酪氨酸激酶活性的受体（tyrosinekinase-linkedreceptors，TKR）结合，向细胞内传递信号。FL3作用于HSC/HPC，通过与在细胞表面的有TKR结合而发挥造血调控作用。FL3也是十分重要的早期祖细胞刺激因子，对HSC/HPC体外扩增有明显的促进作用，能阻止CD34+干细胞在体外扩增时逐渐定向分化，耗净HPC的倾向。● 转化生长因子-β转化生长因子-β、转化生长因子-β1、β2 和 β3 三种哺乳动物亚型通过同一受体发出信号，引起相似的生物学反应。它们是多功能细胞因子，调节细胞增殖、生长、分化和运动，以及细胞外基质的合成和沉积。转化生长因子-β（transforminggrowthfactor-β，TGF-β）由骨髓基质细胞产生，抑制早期HSC/HPC进入S期，使大多数HSC/HPC处于G0期。● 巨噬细胞炎性蛋白-1α巨噬细胞炎性蛋白-1β（MIP-1β）与巨噬细胞炎性蛋白-1α（macrophageinflammatoryprotein1α，MIP-1α）相伴而生，是MIP-1α的天然拮抗剂，可以解除MIP-1α对早期HSC/HPC的抑制作用，阻止HSC重新返回静止状态。● p38p38作为一个信号传递分子属于丝裂原激活蛋白激酶（MAPK）家族的一员，在常氧条件下抑制HSC的体外扩增。有实验表明，当HSC在加有TPO、SCF、FL3的无血清培养液中，由于氧化应激而激活p38和p16，导致鼠HSC数量明显的减少。● 粒-巨噬细胞-集落刺激因子（GM-CSF）粒细胞-巨噬细胞集落刺激因子是临床上用于各种原因引起的白细胞或粒细胞减少症的药物。目前使用的细胞动员剂是“粒一巨噬细胞集落刺激因子（ GM--CSF ）”，GM--CSF除能增加外周血造血干细胞的数量外，还有辅助心脏功能等作用。● 粒细胞-集落刺激因子（G-CSF）粒细胞集落刺激因子的作用一般有抗原呈递、增强巨噬细胞作用、促进造血干细胞增殖等。粒细胞集落刺激因子是骨髓干细胞的强力动员剂，能刺激自体骨髓干细胞增殖，动员骨髓干细胞从骨髓到外周血。● 促红细胞生成素（EPO）红细胞生成素（EPO）是造血分化中的主要刺激因子，能促进造血干细胞向原始红细胞分化、加速幼红细胞的分裂增殖、促进血红蛋白的合成，同时在红细胞诱导分化研究中也发挥重要的作用。造血干细胞具有自我更新和多向分化潜能，不同因子的搭配对造血干细胞的增殖效果不同，利用造血干细胞可定向诱导产生多种细胞，这无疑也给NK细胞的增殖提供了新的思路。目前NK细胞可以由胚胎干细胞、iPSC诱导而来，但是无论是胚胎干细胞还是诱导多能干细胞，他们都要转化为造血干细胞后才能进而分化为NK细胞，所以造血干细胞在这其中扮演了不可或缺的桥梁。由干细胞衍生的NK细胞优点是可以随需随用，同质性强，低细胞因子释放，杀伤活性强，所以市面上至今对于干细胞来源的NK的探索仍然保持着极高的热情，下面是干细胞→NK细胞的有关文献，我们主要关注了文献中提到的因子。一、人胚胎干细胞来源的NK细胞将hESCs与小鼠骨髓基质细胞系M210-B4 在含RPMI 1640的培养基中共培养， 15%胎牛血清， 2 mM l -谷氨酰胺， 1%非必需氨基酸， 1%青霉素/链霉素和0.1 mM β-巯基乙醇，培养基每2 ~ 3天更换1次。17 ~ 20 d后，制备单细胞悬液及CD34+CD45+细胞如前所述分离的细胞转移到与小鼠胎肝来源的基质细胞系共培养AFT024在培养基中含有1:2的杜尔贝可混合物改良Eagle培养基/Ham F12， 20%热灭活人血清AB， 2mM l -谷氨酰胺，1%青霉素/链霉素，5 ng/mL亚硒酸钠，50μM乙醇胺，25μM-巯基乙醇，20 mg/mL抗坏血酸，IL-3，干细胞因子, IL-15, fms样酪氨酸激酶3配体和IL-7。细胞用新鲜培养液培养，每隔5 ~ 6天更换一半培养液。培养30 ~ 35 d，收集细胞，过滤70μm滤波器，并用于进一步分析。二、人多能干细胞来源的NK细胞收集18~21d细胞进行CD34+ CD45+祖细胞富集，10万个CD34+CD45+细胞、1 ml NK细胞、起始细胞因子（白细胞介素IL-3, IL- 7, IL-15，干细胞因子[SCF]和fms样酪氨酸激酶受体-3配体[FLT3L]置于EL08-1D2基质上。每4-5天用0.5 ml含细胞因子的培养基更新NK细胞培养物。在EL08-1D2细胞培养28~35d时检测成熟NK细胞。自从基因治疗的概念提出以来, 造血干细胞一直被认为是理想的靶细胞，造血干细胞移植治疗可以治疗很多血液系统疾病，并且多种恶性血液系统疾病只有造血干细胞移植治疗才有可能彻底治愈，此外，地中海贫血等造血系统的基因遗传疾病，也可通过对造血干细胞基因编辑进行治疗。所以造血干细胞的体外培养工艺变得尤为重要。以下是同立海源关于造血干细胞培养所用到的因子列表，北京同立海源拥有十余年重组蛋白研发生产经验，可提供满足您需求的细胞因子产品，欢迎大家垂询。同立海源干细胞相关因子部分数据展示图1：Recombinant Human GM-CSF stimulates proliferation of TF-1(浓度：ng/ml）图2：Recombinant Human FLT3 Ligand stimulates proliferation of OCI AML-5(浓度：ng/ml）图3：Recombinant Human IL-3 stimulates proliferation of TF-1(浓度：ng/ml)图4：Recombinant Human SCF stimulates proliferation of Mo7e(浓度：ng/ml)扫码申请试用试用说明：1.活动时间：即日起-2023年7月31日；2.活动对象：未订购申请样品的新老终端客户；3.试用规格：50μg/支（GM-CSF、Vitronectin蛋白为100μg/支）；4.免费试用名额有限，每个客户限申请一次，（注：同一导师或同一公司为同一客户，不累计赠送）；5.为了让更多用户享有试用机会，拒绝浪费，每个客户申请试用样品种类不超过5个，每个产品种类限制1支；6.申请要求：申请信息完整，能够近期开展实验；7.其他说明：试用结束后，需反馈试用结果；8.本次活动最终解释权归北京同立海源生物科技有限公司所有。END关于同立海源北京同立海源生物科技有限公司，成立于2011年，专注细胞和基因治疗（CGT）上游GMP级原料试剂研发，致力于为生命科学提供可靠的产品与服务。产品涉及细胞分选磁珠试剂，真核/原核重组蛋白、无血清培养基、细胞培养试剂盒、转染试剂、基因编辑工具酶等。为细胞和基因治疗药物、抗体药物开发、细胞储存等生物制药和IVD领域提供核心原料试剂与服务。公司建有2000m2的研发实验室及GMP级洁净车间，包括真核与原核蛋白表达工程平台、细胞培养技术开发平台、体外诊断试剂生产平台，通过ISO13485和ISO9001双认证，部分产品已获美国FDA DMF备案。

2023-01-09

·医药笔记

金宇博沃润泽：托珠单抗递交上市申请

▎Armstrong国家药监局药品审评中心官网2023年1月7日的公开信息显示，金宇博沃润泽生物技术有限公司的治疗用生物制品托珠单抗注射液申报上市，成为继百奥泰、珠海丽珠之后第三个在国内申报上市的托珠单抗生物类似药。托珠单抗（Tocilizumab）最早由日本中外制药株式会社联合开发，该抗体靶向IL-6受体（IL-6R），商品名雅美罗（Actemra）。托珠单抗采用哺乳动物细胞表达，特异性阻断人白介素6（IL-6）受体从而阻断促炎症反应的细胞因子风暴。在体内，IL-6结合IL-6R和gp130蛋白从而形成三聚体复合物。其中，IL-6R分为膜结合型和可溶型两种形式，但两种形式均引发经典的JAK-STAT信号通路。IL-6引起的下游信号通路，可以产生局部和全身性的炎症反应。因此，对IL-6信号通路的阻断，可以产生“广谱”的临床获益。图片来源-2020 nature review托珠单抗先后于2005、2009、2010、2013年在日本、欧洲、美国和中国获批上市。适应症包括成人类风湿关节炎、多关节幼年特发性关节炎、巨细胞关节炎、全身型幼年特发性关节炎、细胞因子释放综合征。在国内获批的适应症为成人类风湿关节炎、全身型幼年特发性关节炎和细胞因子释放综合征。鉴于托珠单抗在细胞因子风暴控制中的关键作用，并且COVID-19的重症患者的细胞因子风暴造成的炎症反应是造成死亡率的重要因素，在新冠爆发后，国内外启动了多个托珠单抗治疗新冠的临床研究。2022年12月22日，FDA批准了罗氏的托珠单抗原研药用于治疗住院成年患者的新型冠状病毒肺炎。2023年1月3日在顶级医学期刊《美国医学会杂志》（JAMA）上发表的研究数据进一步证明了托珠单抗在危重型新型冠状病毒肺炎治疗中的关键作用。该研究基于4869名重症患者的180天随访结果证明IL-6受体拮抗剂（tocilizumab, sarilumab）可提高重症新型冠状病毒感染者6个月生存率的概率大于99.9%，抗血小板药物提高6个月生存率的概率为95%，研究涉及的其他疗法要么无效，要么可能对患者有害。过去几年，托珠单抗在全球的的销售额均接近或者超过40亿美金。原研药没有放弃创新的脚步，2022年11月21日，中国国家药监局药品审评中心（CDE）官网公示显示，罗氏（Roche）递交了托珠单抗皮下注射液的上市申请，并获得受理。国内研发方面，百奥泰、丽珠集团、金宇博沃润泽、海正药业、均有布局托珠单抗生物仿制药的研发。其中，百奥泰进展最快，于2021年11月8日获NDA受理。丽珠集团紧随其后，于2021年12月22日获NDA受理。未来，随着其适应症的逐渐拓展，托珠单抗的竞争将变得更加激烈。2021年4月，百奥泰将托珠单抗类似药国际化权益授权给Biogen，后者支付3000万美元预付款、9000万美元里程碑金额，以及两位数比例的销售分成。可见托珠单抗类似药的商业价值受到业界认可。公开数据显示，金宇博沃润泽生物技术有限公司是上市公司-金宇生物（生物股份）的全资子公司，目前的产业化基地落地江苏省丹阳市。此次申报上市的托珠单抗生物仿制药，临床批件转让自迈博太科药业。预计在产业化基地建成前，双方将基于MAH指导原则进行生产和商业化销售。

生物类似药上市批准

2022-12-13

·健康元

加大研发投入，健康元拟联合丽珠在武汉设立10亿规模产业投资合资公司

近日，健康元药业集团拟联合子公司丽珠医药集团在武汉市设立合资公司，合计出资10亿元人民币对优质的大健康项目进行战略投资。该投资将有利于进一步加大两家集团产业创新，构建多元化的优质研发创新项目孵化和引进平台，快速丰富公司核心管线产品，进一步提升集团的持续盈利能力。以科技创新为战略基点，以打造高壁垒复杂制剂技术平台为战略目标，健康元集团关注前沿科技及未被满足的临床需求，聚焦创新药及高壁垒复杂制剂，围绕呼吸、消化道、辅助生殖、精神、肿瘤等具有显著临床需求的领域进行了丰富的管线布局，强力打造集团多元的产品矩阵及在研药物管线，发展成为集研发、生产、销售、服务为一体的综合性医药集团公司。根据弗若斯特沙利文的行业报告，2021年健康元集团包括子公司丽珠集团营业收入达159亿元，排名国内综合型上市企业第6位。创新是企业的生命线。近年来，健康元打破研发、审批和生产等壁垒，凭借“舒坦琳”、“丽舒同”、“雾舒”等多款高质量吸入制剂产品，逐步突破细分行业中的发展瓶颈，率先成为在呼吸治疗领域打破海外垄断的头部企业，成功实现现有及在研品种覆盖哮喘和COPD吸入治疗药物的主要类别，并通过国谈、集采等契机快速打开与覆盖国内市场，发展成为国内高端复杂制剂的领跑者。子公司丽珠集团近年来则凭借不断发展完善的生物药平台和高壁垒复杂制剂平台，多项创新研发陆续进入收获期。目前，丽珠注射用重组人绒促性素、注射用醋酸西曲瑞克、新冠抗原检测试剂等产品获批上市，重组新型冠状病毒融合蛋白疫苗“丽康V-01”在北京市、上海市、广东省、江苏省等多地开启加强针接种。此外，丽珠注射用醋酸曲普瑞林微球（一个月缓释）、重组人源化抗人IL-6R单克隆抗体注射液也都顺利报产。根据弗若斯特沙利文的行业报告，2021年健康元集团包括子公司丽珠集团研发投入总额达18.5亿元，排名全国综合型上市企业第5位。设立本次投资合资公司，进一步彰显了健康元与丽珠在大健康领域对研发的重视以及战略布局，是健康元与丽珠集团产业投资布局的进一步提升和提速。过去，健康元和丽珠一直持续关注前沿技术，在医药人工智能（AI）、基因编辑、细胞治疗、小分子与大分子创新药、新型医用材料等领域不断丰富产业链布局、赋能产品管线。集团商务拓展频繁取得丰硕成果，积极参与国际先进技术领域平台公司股权投资，包括全球首家专注巨噬细胞工程化改造的公司Carisma Therapeutics，基因编辑公司Beam Therapeutics，多肽肿瘤疫苗公司Elicio Therapeutics、人工智能肿瘤检测公司LungLife AI等；同时关注和投资中国本土创新企业，包括小分子创新药公司江苏新元素和上海科恩泰、人工智能创新药开发公司英飞智药、创新疫苗开发公司绿竹生物等。在项目引进方面，获得德国LTS透皮制剂大中华区授权、同源康医药公司新一代酪氨酸激酶抑制剂授权等。另外还与上海有机所建立联合实验室开发新一代PROTAC药物，与腾讯量子实验室签订战略合作协议探索人工智能在合成生物学领域的应用。近年来，武汉市综合实力稳步提升，2021年武汉市地区生产总值达到17716.76亿元，十年来年均增长7.4%，经济总量始终位列全国城市前十，中部城市领先。武汉重文兴教，已汇聚92所高校、79名院士、149家国家级创新平台，全球首款新冠病毒灭活疫苗、全国首款第四代三维闪存芯片等重大自主创新成果在武汉问世。东湖高新区作为武汉市科技创新创高地，又称“中国光谷”，1991年被国务院批准为首批国家级高新区，2009年被国务院批准为第二个自主创新示范区，2016年获批为中国(湖北)自由贸易试验区武汉片区。综合实力在全国169个国家级高新区中排名第五，其中知识创造和技术创新能力位居榜首，是全国10家重点建设的“世界一流高科技园区”之一。武汉国家生物产业基地，即光谷生物城，是湖北省、武汉市及东湖高新区聚集发展生命健康产业的核心载体和桥头堡，2022年综合实力位居全国生物产业园区第四名，已聚集辉瑞、国药集团、迈瑞医疗、恒瑞医药、药明康德、华大基因、联影医疗、人福集团等国内外知名企业3000余家。凭借健康元和丽珠集团发展数十年已形成的产业优势和武汉及其周边地区的优质的项目资源，设立合资公司，将有利于集团加强对医药产业上游的布局，寻求优质医药研发资源，进一步提升健康元和丽珠集团的研发实力与核心竞争力优势。转自：每日经济新闻

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