Toshinori Agatsuma
Daiichi Sankyo
CytotoxicityChemical synthesisBiological activityCancerMolecular biologyAntibodyMonoclonalChemistryIn vitroImmunologyIn vivoBicyclic moleculeAntibody-drug conjugateLead compoundCarboxylic acidCamptothecinTrastuzumabExatecanTopoisomerase-I InhibitorDNA Topoisomerase IEthyl esterCancer researchMonoclonal antibodyCell growthStereochemistryMedicineCell cultureBiologyImmune systemCancer cellPharmacology
39Publications
12H-index
994Citations
Publications 39
Newest
#1Daisuke Okajima (Daiichi Sankyo)H-Index: 4
#2Satoru Yasuda (Daiichi Sankyo)H-Index: 3
Last. Reiko Kamei (Daiichi Sankyo)H-Index: 1
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Trophoblast cell surface antigen 2 (TROP2) is highly expressed on various epithelial tumors and correlates with poor prognosis. We developed the novel TROP2-directed antibody-drug conjugate (ADC), Datopotamab deruxtecan (Dato-DXd, DS-1062a), with a potent DNA topoisomerase I inhibitor (DXd), and evaluated its antitumor activity and safety profiles in preclinical models. The pharmacological activity and mechanism of action of Dato-DXd were investigated in several human cancer cell lines and xenog...
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#1Kazuki Satoh (Daiichi Sankyo)H-Index: 7
#2Yoichi Kobayashi (Nagoya University)
Last. Shiho Kozuma (Daiichi Sankyo)H-Index: 6
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Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit antitumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective antitumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective antitumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of mult...
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#1Kenji Iida (Daiichi Sankyo)H-Index: 1
#2Amr H. Abdelhamid Ahmed (Harvard University)
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
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Currently, the only approved treatments for gastrointestinal stromal tumor (GIST) are tyrosine kinase inhibitors (TKIs), which eventually lead to development of secondary resistance mutations in KIT or PDGFRA and disease progression. Herein, we identified G protein-coupled receptor 20 (GPR20) as a novel non-TK target in GIST, developed new GPR20 immunohistochemistry, assessed GPR20 expression in cell lines, PDXs & clinical samples from 2 institutes (USA & Japan). We studied GPR20 expression stra...
3 CitationsSource
#1Kenji IidaH-Index: 1
#2Amr Hesham Abdelhamid (Harvard University)H-Index: 2
Last. Toshinori AgatsumaH-Index: 12
view all 23 authors...
More than 85% of GISTs are driven by activating mutations in KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Currently, the only approved treatments for GIST are KIT directed tyrosine kinase inhibitors (TKIs). However, treatment with approved TKIs eventually results in disease progression most often due to the development of secondary resistance mutations in KIT. In addition, these agents have limited activity in PDGFRA mutant GIST and...
2 CitationsSource
#1Yoshitaka Isumi (Daiichi Sankyo)H-Index: 1
#2Shinko Hayashi (Daiichi Sankyo)H-Index: 6
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
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Purpose Neovascular age-related macular degeneration (nAMD) results from choroidal neovascularization (CNV) and causes severe vision loss. Intravitreal anti-vascular endothelial growth factor (VEGF) therapies have significantly improved therapeutic outcomes; however, a substantial number of patients experience disease progression. Roundabout 4 (ROBO4) has been reported to be a vascular-specific protein that stabilizes vasculature in ocular pathological angiogenesis. To explore ROBO4 targeting as...
1 CitationsSource
#1Anri AkiH-Index: 3
#2Kento TanakaH-Index: 1
Last. Tomoaki Komai (Daiichi Sankyo)H-Index: 4
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ORAI1 constitutes the pore-forming subunit of the calcium release-activated calcium (CRAC) channel, which is responsible for store-operated calcium entry into lymphocytes. It is known that ORAI1 is essential for the activation of T cells and mast cells and is considered to be a potent therapeutic target for autoimmune and allergic diseases. Here, we obtained a new humanized antibody, DS-2741a, that inhibits ORAI1 function. DS-2741a bound to human-ORAI1 with high affinity and without cross-reacti...
3 CitationsSource
#1Daisuke Okajima (Daiichi Sankyo)H-Index: 4
#2Junko Yamaguchi (Daiichi Sankyo)H-Index: 5
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 15 authors...
Background: A trophoblast cell surface antigen 2 (TROP2) is a 36-kDa single-pass transmembrane protein overexpressed in various epithelial tumors including non-small cell lung cancer (NSCLC) with relatively low and restricted expression in normal tissues, and is associated with aggressive tumor behavior. Therefore, TROP2 could be an attractive target for cancer therapy. We created DS-1062a, TROP2-targeting antibody-drug conjugate (ADC) with Daiichi Sankyo DXd technology using a novel DNA topoiso...
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#1Keisuke Fukuchi (Daiichi Sankyo)H-Index: 5
#2Kayoko Nanai (Daiichi Sankyo)
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
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CD147, a type I membrane protein, is highly expressed in various cancers and is involved in the growth, metastasis, and activation of inflammatory signals in cancer cells via interaction with various molecules, such as integrins, CD44, and monocarboxylate transporters. Additionally, the expression of CD147 in tumors positively correlates with poor prognosis in various cancers. Therefore, CD147 is an attractive target for cancer therapy. However, there have been no successful drugs targeting CD14...
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#1Hashimoto Yuuri (Daiichi Sankyo)H-Index: 1
#2Kumiko Koyama (Daiichi Sankyo)H-Index: 8
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
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Purpose: HER3 is a compelling target for cancer treatment; however no HER3-targeted therapy is currently clinically available. Here, we produced U3-1402, an anti-HER3 antibody-drug conjugate with a topoisomerase I inhibitor exatecan -derivative (DXd), and systematically investigated its targeted drug delivery potential and antitumor activity in preclinical models. Experimental Design: In vitro pharmacological activities and the mechanisms of action of U3-1402 were assessed in several human cance...
19 CitationsSource