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疾病领域	数量

肿瘤	2
内分泌与代谢疾病	1

排名前五的药物类型	数量

单克隆抗体	2

排名前五的靶点	数量

TM4SF4	2

关联

2

项与 Algok Bio, Inc. 相关的药物

AGK-102

靶点

TM4SF4

作用机制

TM4SF4 抑制剂

在研机构

Algok Bio, Inc.

原研机构

Algok Bio, Inc.

在研适应症

肝癌 [+2]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

ECL-2B7

靶点

TM4SF4

作用机制

TM4SF4 抑制剂

在研机构

Algok Bio, Inc.

原研机构

Algok Bio, Inc.

在研适应症

非小细胞肺癌

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

100 项与 Algok Bio, Inc. 相关的临床结果

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0 项与 Algok Bio, Inc. 相关的专利（医药）

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1

项与 Algok Bio, Inc. 相关的文献（医药）

2024-03-22·Cancer Research

Abstract 3189: A novel monoclonal antibody targeting TM4SF4 enhances antitumor activity through regulation of cellular levels of immune checkpoint ligands and antibody dependent cellular cytotoxicity

作者: Kahm, Yeon-jee ; Jung, Uhee ; Kim, In-Gyu ; Kim, Rae Kwon ; Kim, Sung-Chul ; Kim, Won-Yong ; Heo, Chang-Kyu ; Ryu, Chun-jeih ; Kim, Bum-Jin ; Cho, Eun-Wie ; Shin, Byung-Chul

AbstractTransmembrane 4 super family member 4(TM4SF4) protein has been shown to be involved in EMT-associated stemness through autocrine of insulin-like growth factor 1(IGF1) and osteopontin(OPN) in non-small cell lung cancer(NSCLC) cells. However, its potential as a therapeutic target has not been evaluated. In this study, anti-human TM4SF4 monoclonal antibodies(anti-hTM4SF4 mAbs) were prepared in mouse as part of a strategy for developing anticancer drug using humanized antibody. A synthetic peptide(15 mer, 126-140th AA) derived from the extracellular loop(ECL) 2 of human TM4SF4 exposed on outer cell surface was used as an immunization antigen. Among the selected anti-hTM4SF4 mAbs, ECL-2B7 and ECL-12A8 showed the best affinity for the antigen(Kd), approximately 2.66 nM and 8.34 nM, as determined by surface plasmon resonance analysis. Using mouse xenograft of NSCLC cell line, it was confirmed that ECL-2B7 was superior to ECL-12A8 in producing humanized antibody. ECL-2B7 inhibited EMT-associated stemness of TM4SF4 positive cancer cells by blocking cellular signaling events such as IGF1Rβ and CD44 and their downstream signals, PI3K/AKT/GSK3β/NF-κB and JAK2/STAT3 pathways. ECL-2B7 also enhanced antitumor activity by downregulating cellular and exosomal level of PD-L1 and B7-H4, immune-checkpoint ligands that elicit immunosuppression of T cell, and by mediating antibody-dependent cellular cytotoxicity. Treatment with OPN- and IGF1-neutralizing antibodies suppressed intracellular PD-L1 and B7-H4 level. It means that the regulation of PD-L1 and B7-H4 levels by TM4SF4 is closely related to the autocrine action of OPN and IGF1 induced by TM4SF4. Using patient-derived xenograft model, it was confirmed that the ECL-2B7 has excellent antitumor activity that effectively inhibits tumor progress. These results strongly suggest that it is necessary to construct humanized antibody based on ECL-2B7 to confirm its potential as a novel anticancer drug.Citation Format: Rae Kwon Kim, Chang-Kyu Heo, Yeon-jee Kahm, Uhee Jung, Byung-Chul Shin, Won-Yong Kim, Bum-Jin Kim, Sung-Chul Kim, Chun-jeih Ryu, Eun-Wie Cho, In-Gyu Kim. A novel monoclonal antibody targeting TM4SF4 enhances antitumor activity through regulation of cellular levels of immune checkpoint ligands and antibody dependent cellular cytotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3189.

100 项与 Algok Bio, Inc. 相关的药物交易

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100 项与 Algok Bio, Inc. 相关的转化医学

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