阿德木单抗(Adecatumumab) - 药物靶点：EpCAM_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Anti-EpCAM mAb MT201、Human anti-EpCAM monoclonal antibody MT201、Monoclonal antibody MT201

+ [3]

靶点

EpCAM

作用方式

抑制剂

作用机制

EpCAM抑制剂(上皮细胞粘附分子抑制剂)、ADCC(抗体依赖的细胞毒作用)

治疗领域

肿瘤消化系统疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症-

非在研适应症

乳腺癌结直肠癌肝转移肝转移+ [1]

原研机构

Amgen, Inc.

在研机构-

非在研机构

Amgen Research (Munich) GmbH

Amgen, Inc.Merck Serono SA

权益机构-

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

结构/序列

Sequence Code 94529H

来源: *****

Sequence Code 211155L

来源: *****

关联

1

项与阿德木单抗相关的临床试验

NCT00866944

/ Completed临床2期

A Randomized, Open-label, Controlled, Multi-center Phase II Study to Evaluate the Efficacy and Safety of Adecatumumab Alone or Sequentially to FOLFOX Relative to FOLFOX After R0 Resection of Colorectal Liver Metastases

The purpose of this study is to determine the effect of adecatumumab alone or following FOLFOX in patients with R0 resected liver metastases from CRC (colorectal carcinoma) and to compare the effect to FOLFOX alone.

开始日期2009-03-01

申办/合作机构

Amgen Research (Munich) GmbH

100 项与阿德木单抗相关的临床结果

登录后查看更多信息

100 项与阿德木单抗相关的转化医学

登录后查看更多信息

100 项与阿德木单抗相关的专利（医药）

登录后查看更多信息

12

项与阿德木单抗相关的文献（医药）

2026-11-01·BIOMEDICINE & PHARMACOTHERAPY

Development and preclinical characterization of an MMAE-conjugated anti-EpCAM antibody–drug conjugate for colorectal cancer

Article

作者: Kong, Deok-Hoon ; Jung, Sang Hoon ; Lee, Jae Wook ; Park, Young-Heon ; Song, Yong Bhum ; Lee, Sungjin ; Kim, Dong-Beom ; Nguyen, Qui Ngoc Sang ; Baek, Si-Eun ; Kim, Se-Hyun ; Ko, Hae Li ; Lee, Wook-Bin

The epithelial cell adhesion molecule (EpCAM) is frequently overexpressed in colorectal cancer (CRC) and thus represents an attractive therapeutic target. However, the clinical efficacy of EpCAM-targeting antibodies has been limited by suboptimal binding properties and reliance on immune effector mechanisms. Here, we describe the development and characterization of anti-EpCAM #126, a fully human monoclonal antibody isolated from the OPAL phage-display library, and its corresponding antibody-drug conjugate (ADC). Anti-EpCAM #126 exhibited substantially higher binding affinity than adecatumumab, primarily owing to a markedly lower dissociation rate. High-density peptide microarray analysis and alanine-scanning mutagenesis identified NGSKLGRRAK (residues 74-83) within the EpCAM extracellular domain as the dominant epitope, with S76, R81, and K83 serving as key contact residues. Binding was conformation-dependent and markedly decreased following trypsin-mediated proteolytic cleavage of the epitope region. Anti-EpCAM #126 demonstrated robust staining of CRC xenograft and patient-derived tumor tissues and exhibited low cytokine release in human peripheral blood mononuclear cells and mouse models. Following the confirmation of efficient receptor-mediated internalization, anti-EpCAM #126 was conjugated to monomethyl auristatin E (MMAE) through a protease-cleavable valine-alanine linker, generating an ADC with a controlled average drug-to-antibody ratio of 4.31 while retaining nanomolar EpCAM-binding affinity. The resulting ADC exhibited potent cytotoxicity against EpCAM-expressing CRC cell lines and achieved 84.96% tumor growth inhibition in a patient-derived xenograft model at 10 mg/kg, whereas the unconjugated antibody showed no antitumor activity. These findings suggest that anti-EpCAM #126-MMAE is a high-affinity, epitope-specific ADC with promising preclinical efficacy against EpCAM-positive CRC.

2025-12-01·CANCER SCIENCE

Near‐Infrared Photoimmunotherapy Targeting Esophagogastric Junction Adenocarcinoma With Fully Human Anti‐ EpCAM Antibody

Article

作者: Shingo Sakashita ; Shuichi Mitsunaga ; Takeo Fujita ; Tomonori Yano ; Hideki Tanaka ; Masahiro Yasunaga ; Takahiro Anzai ; Kenji Takashima ; Shiqi Yang ; Shinji Saijou ; Maasa Sasabe ; Yusuke Yoda ; Yoshikatsu Koga ; Akihiro Ishikawa ; Toru Yamaguchi

ABSTRACT:

Near‐infrared photoimmunotherapy (NIR‐PIT) is a tumor‐specific treatment using monoclonal antibody (mAb) photosensitizer conjugates, followed by near‐infrared light irradiation. This study aimed to identify the optimum target for treating esophagogastric junction (EGJ) adenocarcinoma and to evaluate the efficacy of NIR‐PIT using mAbs in preclinical models. Tumor samples from 46 consecutive patients who had undergone surgery without any prior treatment for EGJ adenocarcinoma were assessed for expression and homogeneity of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and epithelial cell adhesion molecule (EpCAM) through immunohistochemistry. Results showed positive rates of 22%, 13%, and 98% for EGFR, HER2, and EpCAM, respectively, with EpCAM also demonstrating the highest homogeneity (93%). Therefore, EpCAM was selected as the optimal target for NIR‐PIT. The fully human monoclonal antibody targeting EpCAM, adecatumumab, was conjugated with the photosensitizer IR700 at different dye‐antibody ratios (DAR2, DAR4, DAR7) and tested on OE19 cells and xenograft mouse models under near‐infrared light irradiation. NIR‐PIT with adecatumumab‐IR700 significantly reduced tumor size and improved prognoses compared to controls, with DAR2 showing the best balance of efficacy and minimal side effects. Notable EpCAM expression and homogeneity underpin EpCAM as a promising target for NIR‐PIT in EGJ adenocarcinoma. The fully human anti‐EpCAM antibody may be suitable for NIR‐PIT in EGJ adenocarcinoma.

2018-10-17·Current cancer drug targets4区 · 医学

Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update

4区 · 医学

Review

作者: Eyvazi, Shirin ; Zarredar, Habib ; Kanipour, Farzad ; Bandehpour, Mojghan ; Farajnia, Safar ; Dastmalchi, Siavoush

Todays, after four decades from the discovery of monoclonal antibodies by Kohler and Milstein in 1975, a dozen of antibodies are used in cancer targeted therapy with different strategies. The success of these antibodies depends on the specificity of antigens expressed on the cancer cells. Epithelial Cell Adhesion Molecule (EpCAM), a homophilic cell-cell adhesion glycoprotein is a well- known tumor antigen, which expresses on epithelial tumors and circulating tumor cells as well as cancer stem cells. The EpCAM signaling pathway is associated with proliferation, differentiation and adhesion of epithelial cancer cells. Here we review EpCAM structure, expression profile and its signaling pathway in cancer cells. In addition, we focused on structure, mechanism of action and success of anti EpCAM antibodies which have been used in different clinical trials. Based on literatures, Edrecolomab showed limited efficacy in the phase III studies. The wholly human monoclonal antibody Adecatumumab is dose- and target-dependent in metastatic breast cancer patients expressing EpCAM. The chimeric antibody, Catumaxomab, has been approved for the treatment of malignant ascites; however, this Mab showed considerable results in intrapleural administration in cancer patients. Anti EpCAM toxin conjugated antibodies like, Oportuzumab Monatox (scFv antibody and Pseudomonas exotoxin A (ETA)), Citatuzumab Bogatox (Fab fragment with bouganin toxin) and immono-conjugate antibody Tucotuzumab (monoclonal antibody with IL2), have shown acceptable results in different clinical trials. Almost, all of the antibodies were well-tolerated; however, still more clinical trials are needed for the approval of antibodies for the treatment of specific tumors.

1

项与阿德木单抗相关的新闻（医药）

2007-08-30

·BioSpace

Micromet to Present at the Sal. Oppenheim 2nd European Healthcare Conference

BETHESDA, Md., Aug. 30 /PRNewswire-FirstCall/ -- Micromet, Inc. , a biopharmaceutical company focusing on the development of novel, proprietary antibody-based products for cancer, inflammation and autoimmune diseases, today announced that Dr. Christian Itin, President and Chief Executive Officer of Micromet, will present at the Sal. Oppenheim 2nd European Healthcare Conference in Frankfurt, Germany on Wednesday, September 5, 2007 at 9:50am Eastern time (3:50pm central European time). About Micromet, Inc. ( ) Micromet, Inc. is a biopharmaceutical company focusing on the development of novel, proprietary antibody-based products for cancer, inflammation and autoimmune diseases. Three product candidates are currently in clinical trials. MT103, also known as MEDI-538, is the first product candidate based on Micromet's novel BiTE(R) antibody product development platform and is being evaluated in a phase 1 clinical trial for the treatment of patients with non- Hodgkin's lymphoma. The BiTE antibody product development platform is based on a unique, antibody-based class of drugs that leverages the cytotoxic potential of T cells in the treatment of cancer. T cells are the most powerful 'killer cells' of the human immune system. Micromet has established a collaboration with MedImmune, Inc. for MT103/MEDI-538. The second clinical stage product candidate is adecatumumab, also known as MT201, a recombinant human monoclonal antibody which targets EpCAM expressing tumors. Adecatumumab is being developed for the treatment of patients with breast cancer. A phase 2a clinical trial in this indication has been completed and a phase 1b trial evaluating the safety and tolerability of MT201 in combination with docetaxel is currently ongoing in patients with metastatic breast cancer. Our third clinical stage product candidate is D93, also known as TRC093, a first-in- class humanized monoclonal antibody that inhibits angiogenesis and tumor cell growth by binding cleaved collagen. This product candidate is in phase 1 clinical trials and is being developed by TRACON Pharmaceuticals for the treatment of patients with cancer and age-related macular degeneration pursuant to license agreement under which Micromet has granted TRACON the worldwide rights to develop and commercialize D93/TRC093. In addition, Micromet has established a collaboration with Nycomed for the development and commercialization of MT203, Micromet's human antibody neutralizing the activity of granulocyte/macrophage colony stimulating factor (GM-CSF), which has potential applications in the treatment of inflammatory diseases, such as rheumatoid arthritis, as well as autoimmune diseases. Micromet, Inc. CONTACT: Christopher Schnittker, SVP & CFO, Micromet, Inc.,+1-240-752-1421, cschnittker@micromet-inc.com, Investors, Susan Noonan,+1-212-966-3650, susan@sanoonan.com, Patricia Garrison, +1-917-322-2567,pgarrison@rxir.com Web site:

合作抗体

100 项与阿德木单抗相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	阿德木单抗	-	DB05006

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
结直肠癌肝转移	临床2期	法国	Amgen Research (Munich) GmbH	2009-03-01
结直肠癌肝转移	临床2期	德国	Amgen Research (Munich) GmbH	2009-03-01
肝转移	临床2期	法国	Amgen Research (Munich) GmbH	2009-03-01
肝转移	临床2期	德国	Amgen Research (Munich) GmbH	2009-03-01
乳腺癌	临床2期	-	Amgen, Inc.	-
乳腺癌	临床2期	-	Merck Serono SA	-
前列腺癌	临床2期	-	Amgen, Inc.	-
前列腺癌	临床2期	-	Merck Serono SA	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2009	临床1期	转移性乳腺癌	22	MT201 (180 mg/m2)	窪選製糧觸憲壓獵顧膚(醖窪艱憲製願顧艱獵鏇) = 願繭淵獵鹹壓艱鏇製獵衊餘獵艱網積膚獵艱衊 (衊網淵鏇顧鏇繭襯鹹醖 )	-	2009-05-20
				MT201 (550 mg/m2)	窪選製糧觸憲壓獵顧膚(醖窪艱憲製願顧艱獵鏇) = 淵願鹽遞鬱蓋淵糧遞鑰衊餘獵艱網積膚獵艱衊 (衊網淵鏇顧鏇繭襯鹹醖 )
ASCO2007 人工标引	临床2期	转移性乳腺癌	109	adecatumumab (high-level EpCAM expression)	蓋願鏇鹹獵觸網夢簾網(選鹽壓選廠廠鏇築蓋夢) = 餘蓋糧範齋顧憲鏇廠簾壓遞齋醖簾鑰鹹壓壓繭 (積鑰醖範壓醖憲憲選鏇 ) 更多	非优	2007-06-20
				adecatumumab (low-level EpCAM expression)	蓋願鏇鹹獵觸網夢簾網(選鹽壓選廠廠鏇築蓋夢) = 鹹觸醖鏇壓壓淵醖膚鏇壓遞齋醖簾鑰鹹壓壓繭 (積鑰醖範壓醖憲憲選鏇 )
ASCO2004	临床1期	去势抵抗性前列腺癌	20	MT201	夢鏇鬱繭簾齋餘廠襯獵(觸糧鏇築餘糧繭範襯鏇) = 網鬱廠蓋窪壓襯衊構鹹鹽夢鹽簾鏇繭餘築網窪 (願淵鹹醖憲糧鑰鑰齋窪 )	-	2004-07-15