Somatropin biobetter(Nautilus Biotech SA)(Somatropin biobetter(Nautilus Biotech SA))

概要

基本信息

药物类型

生物类似药、激素

别名

HanTropin、Oral hGH、Resist-hGH

+ [5]

靶点

GHR

作用机制

GHR激动剂(生长激素受体激动剂)

治疗领域

神经系统疾病内分泌与代谢疾病其他疾病

在研适应症-

非在研适应症

生长激素缺乏症

原研机构

Nautilus Biotech SA

在研机构-

非在研机构

Nautilus Biotech SA

最高研发阶段终止临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 26401985

当前序列信息引自: *****

关联

100 项与 Somatropin biobetter(Nautilus Biotech SA) 相关的临床结果

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100 项与 Somatropin biobetter(Nautilus Biotech SA) 相关的转化医学

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100 项与 Somatropin biobetter(Nautilus Biotech SA) 相关的专利（医药）

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1

项与 Somatropin biobetter(Nautilus Biotech SA) 相关的文献（医药）

2019-08-01·Cell Research1区 · 生物学

Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy

1区 · 生物学

Article

作者: Zhang, Yan ; Tang, Fei ; Zhang, Peng ; Du, Xuexiang ; Zheng, Pan ; Fields, James K ; Devenport, Martin ; Ai, Chunxia ; Liu, Mingyue ; Liu, Yang ; Latinovic, Olga S ; Sundberg, Eric J

It remains unclear why the clinically used anti-CTLA-4 antibodies, popularly called checkpoint inhibitors, have severe immunotherapy-related adverse effects (irAEs) and yet suboptimal cancer immunotherapeutic effects (CITE). Here we report that while irAE-prone Ipilimumab and TremeIgG1 rapidly direct cell surface CTLA-4 for lysosomal degradation, the non-irAE-prone antibodies we generated, HL12 or HL32, dissociate from CTLA-4 after endocytosis and allow CTLA-4 recycling to cell surface by the LRBA-dependent mechanism. Disrupting CTLA-4 recycling results in robust CTLA-4 downregulation by all anti-CTLA-4 antibodies and confers toxicity to a non-irAE-prone anti-CTLA-4 mAb. Conversely, increasing the pH sensitivity of TremeIgG1 by introducing designed tyrosine-to-histidine mutations prevents antibody-triggered lysosomal CTLA-4 downregulation and dramatically attenuates irAE. Surprisingly, by avoiding CTLA-4 downregulation and due to their increased bioavailability, pH-sensitive anti-CTLA-4 antibodies are more effective in intratumor regulatory T-cell depletion and rejection of large established tumors. Our data establish a new paradigm for cancer research that allows for abrogating irAE while increasing CITE of anti-CTLA-4 antibodies.

100 项与 Somatropin biobetter(Nautilus Biotech SA) 相关的药物交易

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