Toshinori Agatsuma
Daiichi Sankyo
CytotoxicityChemical synthesisBiological activityCancerMolecular biologyAntibodyMonoclonalChemistryIn vitroImmunologyIn vivoBicyclic moleculeAntibody-drug conjugateLead compoundCarboxylic acidCamptothecinTrastuzumabExatecanTopoisomerase-I InhibitorDNA Topoisomerase IEthyl esterCancer researchMonoclonal antibodyCell growthStereochemistryMedicineCell cultureBiologyCancer cellPharmacology
38Publications
12H-index
967Citations
Publications 36
Newest
#1Kenji Iida (Daiichi Sankyo)H-Index: 1
#2Amr H. Abdelhamid Ahmed (Harvard University)
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 24 authors...
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...
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#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...
1 CitationsSource
#1Yoshitaka Isumi (Daiichi Sankyo)H-Index: 1
#2Shinko Hayashi (Daiichi Sankyo)H-Index: 6
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 7 authors...
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...
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#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...
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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...
10 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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#1Tomomi Nakayama Iwata (Daiichi Sankyo)H-Index: 3
#2Kiyoshi Sugihara (Daiichi Sankyo)H-Index: 4
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
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[Fam-] trastuzumab deruxtecan (DS-8201a) is a HER2 (ERBB2)-targeting antibody-drug conjugate, composed of a HER2-targeting antibody and a topoisomerase I inhibitor, exatecan derivative, that has antitumor effects in preclinical xenograft models and clinical trials. Recently, [fam-] trastuzumab deruxtecan was reported to enhance antitumor immunity and was beneficial in combination with an anti–PD-1 antibody in a mouse model. In this study, the antitumor effect of [fam-] trastuzumab deruxtecan in ...
8 CitationsSource
#1Kumiko Koyama (Daiichi Sankyo)H-Index: 8
#2Hashimoto Yuuri (Daiichi Sankyo)H-Index: 1
Last. Masato Murakami (Daiichi Sankyo)H-Index: 1
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Background: Human epidermal growth factor receptor 3 (HER3), a member of the ErbB receptor tyrosine kinase family, is overexpressed in a variety of human cancers and plays an important role in cell proliferation and survival. U3-1402 is a novel HER3-targeting antibody-drug conjugate (ADC) consisting of a fully human anti-HER3 antibody (patritumab), a tetrapeptide-based linker, and a topoisomerase I inhibitor payload. It is currently being investigated in clinical trials for HER3-positive breast ...
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#1Takashi Nakada (Daiichi Sankyo)H-Index: 5
#2Kiyoshi Sugihara (Daiichi Sankyo)H-Index: 4
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 5 authors...
: A major limitation of traditional chemotherapy for cancer is dose-limiting toxicity, caused by the exposure of non-tumor cells to cytotoxic agents. Use of molecular targeted drugs, such as specific kinase inhibitors and monoclonal antibodies, is a possible solution to overcome this limitation and has achieved clinical success so far. Use of an antibody-drug conjugate (ADC) is a rational strategy for improving efficacy and reducing systemic adverse events. ADCs use antibodies selectively to del...
48 CitationsSource