作者: Klausz, Katja ; Günther, Andreas ; Penas, Eva Maria Murga ; Burger, Renate ; Wijdenes, John ; Rose-John, Stefan ; Peipp, Matthias ; Staudinger, Matthias ; Gramatzki, Martin

Interleukin-6 has an important role in the pathophysiology of multiple myeloma where it supports the growth and survival of the malignant plasma cells in the bone marrow. It belongs to a family of cytokines which use the glycoprotein 130 chain for signal transduction, such as oncostatin M or leukemia inhibitory factor. Targeting interleukin-6 in plasma cell diseases is currently evaluated in clinical trials with monoclonal antibodies. Here, efforts were made to elucidate the contribution of interleukin-6 and glycoprotein 130 signaling in malignant plasma cell growth in vivo In the xenograft severe combined immune deficiency model employing our interleukin-6-dependent plasma cell line INA-6, the lack of human interleukin-6 induced autocrine interleukin-6 production and a proliferative response to other cytokines of the glycoprotein 130 family. Herein, mice were treated with monoclonal antibodies against human interleukin-6 (elsilimomab/B-E8), the interleukin-6 receptor (B-R6), and with an antibody blocking glycoprotein 130 (B-R3). While treatment of mice with interleukin-6 and interleukin-6 receptor antibodies resulted in a modest delay in tumor growth, the development of plasmacytomas was completely prevented with the anti-glycoprotein 130 antibody. Importantly, complete inhibition was also achieved using F(ab')2-fragments of monoclonal antibody B-R3. Tumors harbor activated signal transducer and activator of transcription 3, and in vitro, the antibody inhibited leukemia inhibitory factor stimulated signal transducer and activator of transcription 3 phosphorylation and cell growth, while being less effective against interleukin-6. In conclusion, the growth of INA-6 plasmacytomas in vivo under interleukin-6 withdrawal remains strictly dependent on glycoprotein 130, and other glycoprotein 130 cytokines may substitute for interleukin-6. Antibodies against glycoprotein 130 are able to overcome this redundancy and should be explored for a possible therapeutic window.

2016-04-02·Expert Opinion on Emerging Drugs2区 · 医学

Emerging antibodies for the treatment of multiple myeloma

2区 · 医学

Review

作者: Zagouri, Flora ; Terpos, Evangelos ; Dimopoulos, Meletios A ; Kastritis, Efstathios

INTRODUCTIONMonoclonal antibodies mark the beginning of a new era in the context of multiple myeloma (MM) treatment. Numerous antibodies have been tested or are currently in development for patients with MM, in order to improve tolerability and quality of life.AREAS COVEREDThis manuscript reviews emerging antibodies for the treatment of MM i.e. elotuzumab, daratumumab, MOR03087, isatuximab, bevacizumab, cetuximab, siltuximab, tocilizumab, elsilimomab, azintrel, rituximab, tositumomab, milatuzumab, lucatumumab, dacetuzumab, figitumumab, dalotuzumab, AVE1642, tabalumab, pembrolizumab, pidilizumab, nivolumab.EXPERT OPINIONAmongst these antibodies, elotuzumab which targets SLAMF-7 and daratumumab which targets CD38, have been recently approved by FDA for patients with relapsed/refractory MM. Both agents are well tolerated. Multiple clinical trials incorporating these monoclonal antibodies in MM treatment are currently ongoing. Of special interest are the anticipated results of phase III clinical trials with elotuzumab [NCT0189164; NCT01335399; NCT02495922] and daratumumab [NCT02252172; NCT02195479] in newly diagnosed MM patients. Moreover, of great interest are the awaited data on pembrolizumabin combination with pomalidomide and dexamethasone in refractory/relapsed MM patients [NCT02576977] and in combination with lenalidomide and dexamethasone in newly diagnosed MM patients. It seems that the incorporation of monoclonal antibodies will change the landscape of myeloma therapy in the near future.

2015-07-01·Applied Microbiology and Biotechnology3区 · 工程技术

Identification of two novel rabbit hemorrhagic disease virus (RHDV) B cell epitopes and evaluation of its immunoprotection against RHDV

3区 · 工程技术

Article

作者: Huang QianQian ; Jiang Qian ; Hu XiaoLiang ; Liu HuaiRan ; Qu LianDong ; Kong DeSheng ; Yu Zuo ; Wang FengJie ; Liu JiaSen ; Guo DongChun

The VP60 protein of rabbit hemorrhagic disease virus (RHDV) is a structural protein with important roles in viral replication and assembly. In this study, we immunized BALB/c mice with the RHDV-TP strain. Six monoclonal antibodies (mAbs) were selected and characterized by enzyme-linked immunosorbent assay, Western blotting, and indirectly immunofluorescence analysis (IFA). All six mAbs (AD4, AG10, BC9, BE8, BH3, and DE2) had positive reactions with recombinant VP60 as analyzed by IFA, but only two (AG10 and DE2) reacted with denatured RHDV by Western blotting. Fifty-four partially overlapping fragments of the VP60 gene were expressed with His or Glutathione S-transferase (GST) tags to identify the epitopes recognized by AG10 and DE2. These two epitopes were located at the C-terminal of VP60 and were longer (64 and 53 amino acids, respectively) than normal B cell epitopes. However, both AG10 and DE2 also interacted with RHDV2 VP60 expressed in insect cells. Amino acid alignments of the AG10 and DE2 epitope regions between RHDV and RHDV2 VP60 indicated several mutations, suggesting that the epitopes recognized by the mAbs AG10 and DE2 were discontinuous. Epitope immunogenicity was evaluated by inoculating specific pathogen-free rabbits with saline, purified DE2 epitope, or RHDV inactive vaccine. Rabbits immunized with the DE2 epitope developed high levels of RHDV-specific antibodies but no cellular immune response and died after challenge with RHDV-HYD isolate. Despite their lack of neutralizing activity, these mAb reagents and epitopes may have useful clinical applications and will be valuable tools in further studies of the structure and function of the RHDV VP60 protein.

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2022年12月05日化妆品批准证明文件送达信息发布

2022年10月1日起，行政相对人可登录网上办事大厅的法定代表人空间查看电子证照，按照法人空间内相关提示自行打印。序号受理编号产品名称注册人注册证号批准日期备注1GHZTZ2104168悦诗风吟丝柔修颜隔离乳01柔情紫爱茉莉化妆品（上海）有限公司国妆特字202237232022-11-29/2GHZTZ2104169悦诗风吟丝柔修颜隔离乳02奶昔绿爱茉莉化妆品（上海）有限公司国妆特字202237202022-11-29/3GHZTZ2104400道欣染发膏（深闷青亚麻色）广州道欣化妆品科技有限公司国妆特字202237192022-11-29/4GHZTZ2200231chuzhuangliren楚庄丽人美白修护精华液广州市白云莱茵化妆品厂国妆特字202237292022-11-29/5GHZTZ2200232chuzhuangliren楚庄丽人美白淡斑乳液广州市白云莱茵化妆品厂国妆特字202237342022-11-29/6GHZTZ2200237Galancur美白防晒乳 SPF50+广州市白云莱茵化妆品厂国妆特字202237182022-11-29/7GHZTZ2200239乐尚妆美白祛痘精华液广州市白云莱茵化妆品厂国妆特字202237212022-11-29/8GHZTZ2200242郝爱妮美白祛痘精华液广州市白云莱茵化妆品厂国妆特字202237222022-11-29/9GHZTZ2200244美攻芙美白祛印修护乳液广州市白云莱茵化妆品厂国妆特字202237142022-11-29/10GHZTZ2200296乐尚妆美白防晒修护乳 SPF50+ PA+++广州市白云莱茵化妆品厂国妆特字202237122022-11-29/11GHZTZ2200356雅美娜黑亮芳香润黑露广州瀚俪生物科技有限公司国妆特字202237112022-11-29/12GHZTZ2200402私信水感清透隔离防晒乳广东雅丽洁精细化工有限公司国妆特字202237382022-11-29/13GHZTZ2200461汉淇HANQI染发膏（橙金色）广州市邦妮精细化工有限公司国妆特字202237362022-11-29/14GHZTZ2200465纽莱伊美光甘草定美白淡斑双萃精华液深圳市一木国际生物科技有限公司国妆特字202237392022-11-29/15GHZTZ2200475舒蒂雅染发膏(红棕色)广州市采洁化妆品有限公司国妆特字202237262022-11-29/16GHZTZ2200476舒蒂雅染发膏(橙红色)广州市采洁化妆品有限公司国妆特字202237302022-11-29/17GHZTZ2200477舒蒂雅染发膏(青灰色)广州市采洁化妆品有限公司国妆特字202237282022-11-29/18GHZTZ2200478舒蒂雅染发膏(浅灰色)广州市采洁化妆品有限公司国妆特字202237272022-11-29/19GHZTZ2200479舒蒂雅染发膏(紫红色)广州市采洁化妆品有限公司国妆特字202237252022-11-29/20GHZTZ2200480舒蒂雅染发膏(摩卡色)广州市采洁化妆品有限公司国妆特字202237352022-11-29/21GHZTZ2200481舒蒂雅染发膏(金黄色)广州市采洁化妆品有限公司国妆特字202237242022-11-29/22GHZTZ2200482舒蒂雅染发膏(栗子色)广州市采洁化妆品有限公司国妆特字202237332022-11-29/23GHZTZ2200530Dlro染发膏（自然黑）广州市金栢丽保健品有限公司国妆特字202237322022-11-29/24GHZTZ2200603惠彩炫色黑发霜（自然黑）广东惠彩化妆品有限公司国妆特字202237132022-11-29/25GHZTZ2200620米诺克斯动感烫发剂广州千羽化妆品有限公司国妆特字202237172022-11-29/26GHZTZ2200667米诺克斯活力烫发剂广州千羽化妆品有限公司国妆特字202237162022-11-29/27GHZTZ2200714惠彩染发焗油膏（02）广东惠彩化妆品有限公司国妆特字202237152022-11-29/28GHZTZ2200791绿宸染发膏（蓝黑色）广州市白云区美倩日用化妆品厂国妆特字202237312022-11-29/29GHZTZ2200855递欧美白祛斑乳广东美宝化妆品有限公司国妆特字202237372022-11-29/30JHZTZ2101121艾诺碧焕活盈亮乳液株式会社爱茉莉太平洋国妆特进字202206572022-11-29/31JHZTZ2101122艾诺碧焕活盈亮柔肤水株式会社爱茉莉太平洋国妆特进字202206512022-11-29/32JHZTZ2101126兰芝新颜柔雾粉底液 #21N1株式会社爱茉莉太平洋国妆特进字202206592022-11-29/33JHZTZ2101209莱珀妮瑞士轻盈防晒乳液 SPF50瑞士蓓丽护肤系列研究所国妆特进字202206472022-11-29/34JHZTZ2101264薇蒂艾儿玫瑰精萃养肤妆前乳LG生活健康股份有限公司国妆特进字202206502022-11-29/35JHZTZ2101337魅可丝柔持久遮瑕膏19化妆艺术有限公司国妆特进字202206482022-11-29/36JHZTZ2101338魅可丝柔持久遮瑕膏26化妆艺术有限公司国妆特进字202206562022-11-29/37JHZTZ2101339魅可丝柔持久遮瑕膏14化妆艺术有限公司国妆特进字202206532022-11-29/38JHZTZ2101373普柔玛丝特染发膏（一） E SG-6（配合普柔双氧乳 2%）朋友株式会社国妆特进字202206442022-11-29/39JHZTZ2101374普柔玛丝特染发膏（一） E BE-8（配合普柔双氧乳 2%）朋友株式会社国妆特进字202206342022-11-29/40JHZTZ2101375普柔玛丝特染发膏（一） MT-7/6（配合普柔双氧乳 6%）朋友株式会社国妆特进字202206392022-11-29/41JHZTZ2101376普柔玛丝特染发膏（一） SV-6（配合普柔双氧乳 2%）朋友株式会社国妆特进字202206462022-11-29/42JHZTZ2101377普柔玛丝特染发膏（一） E NA-3（配合普柔双氧乳 2%）朋友株式会社国妆特进字202206432022-11-29/43JHZTZ2101378普柔玛丝特染发膏（一） E BR-6（配合普柔双氧乳 2%）朋友株式会社国妆特进字202206422022-11-29/44JHZTZ2101379普柔玛丝特染发膏（一） EG-6（配合普柔双氧乳 2%）朋友株式会社国妆特进字202206382022-11-29/45JHZTZ2101380普柔玛丝特染发膏（一） A-7/6（配合普柔双氧乳 6%）朋友株式会社国妆特进字202206402022-11-29/46JHZTZ2101381普柔玛丝特染发膏（一） CB-5（配合普柔双氧乳 2%）朋友株式会社国妆特进字202206352022-11-29/47JHZTZ2101382普柔玛丝特染发膏（一） BB-1（配合普柔双氧乳 2%）朋友株式会社国妆特进字202206452022-11-29/48JHZTZ2101383普柔玛丝特染发膏（一） MT-6/5（配合普柔双氧乳 6%）朋友株式会社国妆特进字202206372022-11-29/49JHZTZ2101385普柔玛丝特染发膏（一） M-10/10（配合普柔双氧乳 6%）朋友株式会社国妆特进字202206362022-11-29/50JHZTZ2101386普柔玛丝特染发膏（一） M-9/9（配合普柔双氧乳 6%）朋友株式会社国妆特进字202206412022-11-29/51JHZTZ2200117FAIRLUCENT 焕白隔离霜 SPF30 PA+++日本美伊娜多化妆品株式会社国妆特进字202206582022-11-29/52JHZTZ2200135花王莉婕泡沫染发剂 LAW26花王株式会社国妆特进字202206552022-11-29/53JHZTZ2200136花王莉婕泡沫染发剂 LAW27花王株式会社国妆特进字202206522022-11-29/54JHZTZ2200138歌薇依芙中性烫发剂 2号德国花王有限公司国妆特进字202206542022-11-29/55JHZTZ2200139歌薇依芙中性烫发剂 1号德国花王有限公司国妆特进字202206602022-11-29/56JHZTZ2200144肌司研德玛修护倍护防晒气垫吉珀可莱集团国妆特进字202206492022-11-29/

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适应症	最高研发状态	国家/地区	公司	日期
多发性骨髓瘤	临床2期	-	Orphan Pharma International	-
多发性骨髓瘤	临床2期	-	Aop Orphan Pharmaceuticals GmbH	-
多发性骨髓瘤	临床2期	-	Aop Orphan Pharmaceuticals GmbH	-
多发性骨髓瘤	临床2期	法国	EUSA Pharma SAS	-
多发性骨髓瘤	临床2期	-	Orphan Pharma International	-
多发性骨髓瘤	临床2期	法国	EUSA Pharma SAS	-
移植后淋巴增生性疾病	临床2期	法国	EUSA Pharma SAS	-