更新于：2024-12-12
Ginisortamab
更新于：2024-12-12
概要
基本信息
非在研机构- |
最高研发阶段临床1/2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 315654010L
来源: *****
Sequence Code 315654012H
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关联
1
项与 Ginisortamab 相关的临床试验A Phase 1/2 Open-Label, Multicenter Study to Assess the Safety, Pharmacokinetics, and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors
100 项与 Ginisortamab 相关的临床结果
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100 项与 Ginisortamab 相关的转化医学
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100 项与 Ginisortamab 相关的专利（医药）
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11
项与 Ginisortamab 相关的文献（医药）2023-12-31mAbs
Discovery of ginisortamab, a potent and novel anti-gremlin-1 antibody in clinical development for the treatment of cancer
Article
作者: Kevorkian, Lara ; Jones, Paul S ; Rowley, Tania F ; Ottone, Cristina ; Wright, Michael ; Davies, Gareth C G ; Schulze, Monika-Sarah E D ; Dedi, Neesha ; Scott-Tucker, Anthony ; McMillan, David ; Tewari, Roohi ; West, Shauna
Gremlin-1, a high-affinity antagonist of bone morphogenetic proteins (BMP)-2, -4, and -7, is implicated in tumor initiation and progression. Increased gremlin-1 expression, and therefore suppressed BMP signaling, correlates with poor prognosis in a range of cancer types. A lack of published work using therapeutic modalities has precluded the testing of the hypothesis that blocking the gremlin-1/BMP interaction will provide benefits to patients. To address this shortfall, we developed ginisortamab (UCB6114), a first-in-class clinical anti-human gremlin-1 antibody, currently in clinical development for the treatment of cancer, along with its murine analog antibody Ab7326 mouse immunoglobulin G1 (mIgG1). Surface plasmon resonance assays revealed that ginisortamab and Ab7326 mIgG1 had similar affinities for human and mouse gremlin-1, with mean equilibrium dissociation constants of 87 pM and 61 pM, respectively. The gremlin-1/Ab7326 antigen-binding fragment (Fab) crystal structure revealed a gremlin-1 dimer with a Fab molecule bound to each monomer that blocked BMP binding. In cell culture experiments, ginisortamab fully blocked the activity of recombinant human gremlin-1, and restored BMP signaling pathways in human colorectal cancer (CRC) cell lines. Furthermore, in a human CRC - fibroblast co-culture system where gremlin-1 is produced by the fibroblasts, ginisortamab restored BMP signaling in both the CRC cells and fibroblasts, demonstrating its activity in a relevant human tumor microenvironment model. The safety and efficacy of ginisortamab are currently being evaluated in a Phase 1/2 clinical trial in patients with advanced solid tumors (NCT04393298).
2022-02-18International journal of ophthalmology4区 · 医学
Inhibitory effect on subretinal fibrosis by anti-placental growth factor treatment in a laser-induced choroidal neovascularization model in mice
4区 · 医学
ArticleOA
作者: Liao, Ding-Ying ; Zhou, Ai-Yi ; Yang, Xi-Ting ; Wang, Jian-Ming ; Zhang, Yi ; Wang, Li-Jun
AIM: To investigate whether anti-placental growth factor (PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells.
METHODS: Subretinal fibrosis model was established in laser induced choroidal neovascularization (CNV) mice on day 21 after laser photocoagulation. Immunofluorescence staining (IFS) of cryosections and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of PGF. IFS of whole choroidal flat-mounts was used to detect the degree of subretinal fibrosis. IFS of cryosections and ELISA were used to detect the expression of EMT related indicators in subretinal fibrosis lesions.
RESULTS: The expression of PGF protein in subretinal fibrosis lesions was significantly up-regulated (P<0.05), and mainly co-stained with pan-cytokeratin labeled RPE cells. Intravitreal injection of anti-PGF neutralizing antibody reduced the area of subretinal fibrosis and the ratio of fibrotic/angiogenic area significantly at the concentrations of 0.25, 0.5, 1.0, and 2.0 μg/μL (all P<0.05). The expression of E-cadherin in the local RPE cells decreased, while α-SMA increased significantly in subretinal fibrosis lesions, and the application of anti-PGF neutralizing antibody could reverse these changes (P<0.05).
CONCLUSION: The expression of PGF is up-regulated in the lesion site of subretinal fibrosis and mainly expressed in RPE cells. Intravitreal injection of anti-PGF neutralizing antibody can significantly inhibit the degree of subretinal fibrosis in CNV mice, and this effect may be mediated by the inhibition of PGF on EMT of RPE cells.
2015-11-01Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery
[EPIDERMAI GROWTH FACTOR SECRETED BY ASTROCYTES STIMULATED WITH TACROLIMUS PROMOTING NEURITE OUTGROWTH].
Article
作者: Ge, Yingbin ; Cao, Xiaojian ; Cai, Jun ; Sun, Yu
OBJECTIVE:
To illustrate the role of epidermal growth factor (EGF) secreted by astrocytes in the process of tacrolimus (FK506) in promoting neurite outgrowth.
METHODS:
The spinal cord astrocytes and neuronal cells were isolated respectively from 2-day-old Sprague Dawley (SD) rats and 15-day SD pregnant rats, and cultured in vitro and identified by immunofluorescence staining. The spinal cord astrocytes were cultured with 20 µmol/L FK506 medium in the experimental group, and with FK506 free medium in the control group. The supernatant was collected after 24 hours for preparing conditioned medium, and astrocytes were collected. EGF proteins in the conditioned medium were detected with ELISA, and EGF gene expressions of astrocytes were detected with real-time quantitative PCR (RT-qPCR). The spinal cord neurons were cultured respectively with conditioned medium from the experimental group (FK506-CM) and the control group (C-CM) in group A and group B, also with neutralized C-CM and neutralized FK506-CM with anti-EGF neutralizing antibodies in group C and group D. Both the total neurite length and the longest neurite length were measured and compared among groups.
RESULTS:
Both astrocytes and neurons were confirmed by immunofluorescence staining. The EGF content of experimental group (0.241 ± 0.044) was significantly higher than that of the control group (0.166 ± 0.014) (t = 3.93, P = 0.01); EGF gene expression of the experimental group (1.12 ± 0.25) was significantly higher than that of the control group (0.46 ± 0.11) (t = 5.78, P = 0.00). The neurite length measurement displayed that the total neurite length and the longest neurite length of groups C and D were significantly shorter than those of groups A and B (P < 0.05). Both the total and longest neurite length of group A were significantly longer than those of group B (P < 0.05), but no significant difference was shown between groups C and D (P > 0.05).
CONCLUSION:
The EGF secreted by spinal cord astrocytes can promote the neurite outgrowth. So spinal cord astrocytes can be used as an important intermediary target of FK506 to promote the recovery of neurological function.
1
项与 Ginisortamab 相关的新闻（医药）
100 项与 Ginisortamab 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 实体瘤 | 临床2期 | 比利时 | 2022-01-30 | |
| 晚期恶性实体瘤 | 临床2期 | 美国 | 2020-07-09 | |
| 晚期恶性实体瘤 | 临床2期 | 英国 | 2020-07-09 |
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