Last update 01 Nov 2024

CD47 x αvβ3

Last update 01 Nov 2024

Basic Info

Related Targets

CD47αvβ3

Drugs associated with CD47 x αvβ3

WO2024174743

Patent Mining

Target

CD47 x αvβ3

Mechanism-

Active Org.

Hengyi Biomedicine (Shanghai) Co., Ltd.

Originator Org.

Hengyi Biomedicine (Shanghai) Co., Ltd.

Active Indication

Respiratory Tract Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CD47 x αvβ3

100 Translational Medicine associated with CD47 x αvβ3

0 Patents (Medical) associated with CD47 x αvβ3

Literatures (Medical) associated with CD47 x αvβ3

07 Feb 2020·EMBO Molecular Medicine

Endothelial MT 1‐ MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis

Article

Author: Gisbert, Javier P ; Koziol, Agnieszka ; Chaparro, María ; Rius, Cristina ; Arroyo, Alicia G ; Seiki, Motoharu ; Andrés, Vicente ; Urzainqui, Ana ; Gonzalo, Pilar ; Linares, Pablo M ; Clemente, Cristina ; Martínez, Fernando ; Esteban, Sergio

Pathological angiogenesis contributes to cancer progression and chronic inflammatory diseases. In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a poorly characterized mechanism involving increased blood flow and splitting of pre-existing capillaries. In this report, mice lacking the protease MT1-MMP in endothelial cells (MT1^iΔ^EC ) presented limited IA in the capillary plexus of the colon mucosa assessed by 3D imaging during 1% DSS-induced colitis. This resulted in better tissue perfusion, preserved intestinal morphology, and milder disease activity index. Combined in vivo intravital microscopy and lentiviral rescue experiments with in vitro cell culture demonstrated that MT1-MMP activity in endothelial cells is required for vasodilation and IA, as well as for nitric oxide production via binding of the C-terminal fragment of MT1-MMP substrate thrombospondin-1 (TSP1) to CD47/αvβ3 integrin. Moreover, TSP1 levels were significantly higher in serum from IBD patients and in vivo administration of an anti-MT1-MMP inhibitory antibody or a nonamer peptide spanning the αvβ3 integrin binding site in TSP1 reduced IA during mouse colitis. Our results identify MT1-MMP as a new actor in inflammatory IA and a promising therapeutic target for inflammatory bowel disease.

01 Oct 2019·Cancer ResearchQ1 · MEDICINE

Arming Tumor-Associated Macrophages to Reverse Epithelial Cancer Progression

Q1 · MEDICINE

Article

Author: Wettersten, Hiromi I. ; Weis, Sara M. ; Pathria, Paulina ; Varner, Judith A. ; Minami, Toshiyuki ; Cheresh, David A. ; Von Schalscha, Tami

AbstractTumor-associated macrophages (TAM) are highly expressed within the tumor microenvironment of a wide range of cancers, where they exert a protumor phenotype by promoting tumor cell growth and suppressing antitumor immune function. Here, we show that TAM accumulation in human and mouse tumors correlates with tumor cell expression of integrin αvβ3, a known driver of epithelial cancer progression and drug resistance. A monoclonal antibody targeting αvβ3 (LM609) exploited the coenrichment of αvβ3 and TAMs to not only eradicate highly aggressive drug-resistant human lung and pancreas cancers in mice, but also to prevent the emergence of circulating tumor cells. Importantly, this antitumor activity in mice was eliminated following macrophage depletion. Although LM609 had no direct effect on tumor cell viability, it engaged macrophages but not natural killer (NK) cells to induce antibody-dependent cellular cytotoxicity (ADCC) of αvβ3-expressing tumor cells despite their expression of the CD47 “don't eat me” signal. In contrast to strategies designed to eliminate TAMs, these findings suggest that anti-αvβ3 represents a promising immunotherapeutic approach to redirect TAMs to serve as tumor killers for late-stage or drug-resistant cancers.Significance:Therapeutic antibodies are commonly engineered to optimize engagement of NK cells as effectors. In contrast, LM609 targets αvβ3 to suppress tumor progression and enhance drug sensitivity by exploiting TAMs to trigger ADCC.

19 Sep 2019·JCI InsightQ1 · MEDICINE

Dysregulated integrin αVβ3 and CD47 signaling promotes joint inflammation, cartilage breakdown, and progression of osteoarthritis

Q1 · MEDICINE

ArticleOA

Author: Elliott, Eileen E ; Cheng, Zhen ; Wang, Qian ; Lepus, Christin M ; Onuma, Kazuhiro ; Sokolove, Jeremy ; Cisar, Cecilia T ; Robinson, William H ; Cao, Richard Rl ; Lingampalli, Nithya ; Giori, Nicholas J ; Bloom, Michelle S ; Liu, Changhao ; Prohaska, Susan S ; Sharpe, Orr ; Sohn, Dong Hyun ; Mao, Rong ; Hu, Nick ; Chu, Constance R ; Weissman, Irving L ; Zhao, Xiaoyan ; Raghu, Harini ; Willingham, Stephen B ; Wong, Heidi

Osteoarthritis (OA) is the leading cause of joint failure, yet the underlying mechanisms remain elusive, and no approved therapies that slow progression exist. Dysregulated integrin function was previously implicated in OA pathogenesis. However, the roles of integrin αVβ3 and the integrin-associated receptor CD47 in OA remain largely unknown. Here, transcriptomic and proteomic analyses of human and murine osteoarthritic tissues revealed dysregulated expression of αVβ3, CD47, and their ligands. Using genetically deficient mice and pharmacologic inhibitors, we showed that αVβ3, CD47, and the downstream signaling molecules Fyn and FAK are crucial to OA pathogenesis. MicroPET/CT imaging of a mouse model showed elevated ligand-binding capacities of integrin αVβ3 and CD47 in osteoarthritic joints. Further, our in vitro studies demonstrated that chondrocyte breakdown products, derived from articular cartilage of individuals with OA, induced αVβ3/CD47-dependent expression of inflammatory and degradative mediators, and revealed the downstream signaling network. Our findings identify a central role for dysregulated αVβ3 and CD47 signaling in OA pathogenesis and suggest that activation of αVβ3 and CD47 signaling in many articular cell types contributes to inflammation and joint destruction in OA. Thus, the data presented here provide a rationale for targeting αVβ3, CD47, and their signaling pathways as a disease-modifying therapy.

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