Imalumab(Imalumab) - 药物靶点：MIF_在研适应症：腹水，结直肠癌_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Anti-MIF monoclonal antibody、Immunoglobulin g1-kappa, anti-(homo sapiens mif (macrophage migration inhibitory factor, glycosylation-inhibiting factor, glif, gif)), homo sapiens monoclonal antibody

+ [1]

靶点

MIF

作用方式

抑制剂、调节剂

作用机制

MIF抑制剂(巨噬细胞移动抑制因子抑制剂)、免疫调节剂

治疗领域

肿瘤消化系统疾病其他疾病

在研适应症

腹水结直肠癌

非在研适应症

狼疮性肾炎恶性腹水转移性结直肠癌+ [2]

原研机构

Cytokine PharmaSciences, Inc.

在研机构

Cytokine PharmaSciences, Inc.

Baxalta, Inc.

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 9057749L

来源: *****

Sequence Code 9057845H

来源: *****

关联

4

项与 Imalumab 相关的临床试验

EUCTR2015-003492-29-HU

/ Not yet recruiting临床1/2期

A Phase 1/2a, Open-Label, Parallel, Two-Arm, Dose-EscalationStudy to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of BAX69 in Subjects with Refractory Ovarian Cancer with Malignant Ascites - Phase 1/2a Two-Arm, Dose-Escalation of BAX69 in subjects with Malignant Ascites of Ovarian Cancer

开始日期2016-03-02

申办/合作机构

Baxalta Innovations GmbH

NCT02540356

/ Terminated临床1/2期

A Phase 1/2a, Open-Label, Parallel, Two-Arm Dose-Escalation Study to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of BAX69 in Subjects With Refractory Ovarian Cancer With Malignant Ascites

The purpose of this study is to evaluate the safety and tolerability of BAX69 monotherapy given either as intraperitoneal (IP) infusion (Single-Route Arm); or as IP infusion after intravenous (IV) infusion (IV+IP) (Double-Route Arm), and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for each Arm separately, in subjects with refractory ovarian cancer and recurrent malignant ascites. In both Arms, the plasma pharmacokinetics (PK) of BAX69 will be characterized, and pharmacodynamics (PD) markers will be explored in plasma and ascites. Two expansion cohorts will further assess the tolerability of the RP2D and explore clinical signs of efficacy.

开始日期2015-11-02

申办/合作机构

Baxalta, Inc.

NCT02448810

/ Terminated临床2期

A Phase 2a Randomized, Open-label Study to Assess the Safety, Tolerability, and Efficacy of BAX69 in Combination With 5-FU/Leucovorin or Panitumumab Versus Standard of Care in Subjects With Metastatic Colorectal Cancer

The purpose of this study is to evaluate the safety and tolerability of BAX69 in combination with 5-fluorouracil (5-FU)/leucovorin (LV) or panitumumab to determine the recommended phase II dose (RP2D) of each combination; and to compare the efficacy between BAX69 in combination with 5-FU/LV for subjects with KRAS or NRAS mutated tumor (mt) or panitumumab, for subjects with KRAS and NRAS wild type tumor (wt) and standard of care (SoC) per investigator choice as third or fourth treatment line in subjects with progressive measurable metastatic colorectal cancer (mCRC).

开始日期2015-06-15

申办/合作机构

Baxalta, Inc.

100 项与 Imalumab 相关的临床结果

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100 项与 Imalumab 相关的转化医学

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100 项与 Imalumab 相关的专利（医药）

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43

项与 Imalumab 相关的文献（医药）

2025-01-01·Translational Oncology

Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells

Article

作者: Zhou, Qi ; Yue, Zhen-Qi ; Fan, Luo-Jun ; Yue, Zhen- Qi ; Xin, Lin ; Zou, Yong-Hui ; Liu, Jiang ; Xu, He-Song ; Lai, Jun-Yan ; Gan, Jin-Heng

BACKGROUNDThe limited curative effect of PD-L1/PD-1 blockades presents challenges to immunotherapy for advanced gastric cancer. We have found that methionine restriction (MR) enhances the drug resistance of gastric carcinoma cells. We aimed to explore whether MR can enhance the efficacy of PD-L1/PD-1 blockades in gastric cancer.METHODSTo conduct MR, gastric carcinoma cells were transfected with LV-METase in vitro, and 615 mice were injected with MFC cells with stable METase expression in vivo. Flow cytometry was conducted to measure the proportions of M1/M2 macrophages and CD8⁺ GZMB⁺/IFN-γ⁺ T cells. Additionally, the levels of M1/M2 macrophage markers and MIF were also detected.RESULTSMR increased M1 and down-regulated M2 macrophages. MR suppressed MIF levels in gastric carcinoma cells, while the addition of anti-MIF neutralizing antibody inhibited the effect of MR on macrophage M1/M2 polarization. MR enhanced the increase of the proportion of CD8⁺ GZMB⁺ T cells and CD8⁺ IFN-γ⁺ T cells induced by PD-L1/PD-1 blockades. In vivo detection verified the efficacy of the combination of MR and PD-L1/PD-1 blockades on gastric cancer.CONCLUSIONSMR inhibits the secretion of MIF by gastric carcinoma cells, promotes macrophage M1 polarization, and enhances the therapeutic effect of PD-L1/PD-1 blockades in gastric cancer.

2023-05-04·Molecular cancer therapeutics

Preclinical Evaluation of ON203, A Novel Bioengineered mAb Targeting Oxidized Macrophage Migration Inhibitory Factor as an Anticancer Therapeutic.

Article

作者: Mirkina, Irina ; Kerschbaumer, Randolf J ; Maurer, Barbara ; Rossmueller, Gregor ; Mayer, Julia ; Hoeld, Verena ; Schinagl, Alexander ; Thiele, Michael

High levels of macrophage migration inhibitory factor (MIF) in patients with cancer are associated with poor prognosis. Its redox-dependent conformational isoform, termed oxidized MIF (oxMIF), is a promising tumor target due to its selective occurrence in tumor lesions and at inflammatory sites. A first-generation anti-oxMIF mAb, imalumab, was investigated in clinical trials in patients with advanced solid tumors, where it was well tolerated and showed signs of efficacy. However, imalumab has a short half-life in humans, increased aggregation propensity, and an unfavorable pharmacokinetic profile. Here, we aimed to optimize imalumab by improving its physicochemical characteristics and boosting its effector functions. Point mutations introduced into the variable regions reduced hydrophobicity and the antibodies' aggregation potential, and increased plasma half-life and tumor accumulation in vivo, while retaining affinity and specificity to oxMIF. The introduction of mutations into the Fc region known to increase antibody-dependent cellular cytotoxicity resulted in enhanced effector functions of the novel antibodies in vitro, whereas reduced cytokine release from human peripheral blood mononuclear cells in the absence of target antigen by the engineered anti-oxMIF mAb ON203 versus imalumab reveals a favorable in vitro safety profile. In vivo, ON203 mAb demonstrated superior efficacy over imalumab in both prophylactic and established prostate cancer (PC3) mouse xenograft models. In summary, our data highlight the potential of the second-generation anti-oxMIF mAb ON203 as a promising immunotherapy for patients with solid tumors, warranting clinical evaluation.

2021-12-01·Journal of Clinical Investigation1区 · 医学

MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model

1区 · 医学

Article

作者: Pantouris, Georgios ; Fingerle-Rowson, Günter ; Holowka, Thomas ; Tilstam, Pathricia Veronica ; Schulte, Wibke ; Sauler, Maor ; Nouws, Jessica ; Bucala, Richard ; Leng, Lin ; Bernhagen, Jürgen ; Lolis, Elias ; Piecychna, Marta ; Kim, Bong-Sung

Excessive inflammation drives the progression from sepsis to septic shock. Macrophage migration inhibitory factor (MIF) is of interest because MIF promoter polymorphisms predict mortality in different infections, and anti-MIF antibody improves survival in experimental models when administered 8 hours after infectious insult. The recent description of a second MIF superfamily member, D-dopachrome tautomerase (D-DT/MIF-2), prompted closer investigation of MIF-dependent responses. We subjected Mif-/- and Mif-2-/- mice to polymicrobial sepsis and observed a survival benefit with Mif but not Mif-2 deficiency. Survival was associated with reduced numbers of small peritoneal macrophages (SPMs) that, in contrast to large peritoneal macrophages (LPMs), were recruited into the peritoneal cavity. LPMs produced higher quantities of MIF than SPMs, but SPMs expressed higher levels of inflammatory cytokines and the MIF receptors CD74 and CXCR2. Adoptive transfer of WT SPMs into Mif-/- hosts reduced the protective effect of Mif deficiency in polymicrobial sepsis. Notably, MIF-2 lacks the pseudo-(E)LR motif present in MIF that mediates CXCR2 engagement and SPM migration, supporting a specific role for MIF in the recruitment and accumulation of inflammatory SPMs.

100 项与 Imalumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Imalumab	-	DB15558

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
腹水	临床2期	-	Cytokine PharmaSciences, Inc.	-
腹水	临床2期	-	Baxalta, Inc.	-
结直肠癌	临床2期	-	Cytokine PharmaSciences, Inc.	-
恶性腹水	临床前	美国	Baxalta, Inc.	2015-11-02
卵巢癌	临床前	美国	Baxalta, Inc.	2015-11-02
难治性卵巢癌	临床前	美国	Baxalta, Inc.	2015-11-02
转移性结直肠癌	临床前	美国	Baxalta, Inc.	2015-06-15
狼疮性肾炎	临床前	-	Cytokine PharmaSciences, Inc.	-

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临床结果

适应症

分期

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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


NCT02540356 (CTgov)	临床1/2期	难治性卵巢癌 \| 恶性腹水	2	BAX69 Single-Route Arm (Single-Route Arm)	壓簾顧膚鹽窪鑰鹹膚範(顧顧顧艱範齋衊憲窪積) = 餘築衊糧齋艱構獵製鹽襯構觸簾網艱鑰構夢壓 (鹽壓選獵繭構繭顧鏇壓, 蓋範糧網鹹鬱壓願餘醖 ~ 廠餘蓋簾蓋夢製鑰餘鹹) 更多	-	2017-06-15
				BAX69 Double-Route Arm (Double-Route Arm)	壓簾顧膚鹽窪鑰鹹膚範(顧顧顧艱範齋衊憲窪積) = 範積製鏇糧鏇製鏇築衊襯構觸簾網艱鑰構夢壓 (鹽壓選獵繭構繭顧鏇壓, 衊鏇鹹夢遞鹽選網蓋襯 ~ 襯憲觸艱製艱鏇獵鏇鏇) 更多