Yusuke Ogitani
Daiichi Sankyo
PharmacokineticsCancerInternalizationTopoisomeraseCellAntibodyMHC class IChemistryConjugateIn vitroImmunologyIn vivoPatritumabAntibody-drug conjugateCamptothecinTrastuzumabExatecanTopoisomerase-I InhibitorMultidrug resistance-associated protein 2Cancer researchAbcg2Cell growthMedicineCell cultureBiologyImmune systemCancer cellPharmacology
Publications 15
#1Mikiko Suzuki (National Cancer Research Institute)
#2Shigehiro YagishitaH-Index: 10
Last. Akinobu Hamada (National Cancer Research Institute)H-Index: 3
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Purpose: We assessed the intra-tumor pharmacokinetics of [fam-] trastuzumab deruxtecan, T-DXd (known as DS-8201a), a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC), using phosphor-integrated dots (PID) imaging analysis to elucidate its pharmacologic mechanism. Experimental design: We used two mouse xenograft models administered T-DXd at the concentration of 4 mg/kg: (i) a heterogeneous model in which HER2-positive and -negative cell lines were mixed,...
#1Hiromi Okamoto (Daiichi Sankyo)H-Index: 2
#2Masataka Oitate (Daiichi Sankyo)H-Index: 10
Last. Hiroshi Kuga (Daiichi Sankyo)H-Index: 7
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Trastuzumab deruxtecan (T-DXd, DS-8201a) is an antibody-drug conjugate (ADC), comprising an anti-HER2 antibody (Ab) at a drug-to-Ab ratio of 7-8 with the topoisomerase I inhibitor DXd. In this study, we investigated the pharmacokinetics (PK), biodistribution, catabolism, and excretion profiles of T-DXd in HER2-positive tumour-bearing mice.Following intravenous (iv) administration of T-DXd, the PK profiles of T-DXd and total Ab (the sum of conjugated and unconjugated Ab) were almost similar, indi...
5 CitationsSource
#1Hashimoto Yuuri (Daiichi Sankyo)H-Index: 1
#2Kumiko Koyama (Daiichi Sankyo)H-Index: 8
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 23 authors...
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
#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 ...
#1Tomomi Nakayama Iwata (Daiichi Sankyo)H-Index: 3
#2Chiaki Ishii (Daiichi Sankyo)H-Index: 3
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 6 authors...
Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate with a topoisomerase I inhibitor exatecan derivative (DX-8951 derivative, DXd), has been reported to exert potent antitumor effects in xenograft mouse models and clinical trials. In this study, the immune system-activating ability of DS-8201a was assessed. DS-8201a significantly suppressed tumor growth in an immunocompetent mouse model with human HER2-expressing CT26.WT (CT26.WT-hHER2) cells. Cured immunocompetent mice r...
44 CitationsSource
#1Toshihiko DoiH-Index: 62
#2Kohei ShitaraH-Index: 46
Last. Kenji TamuraH-Index: 32
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Summary Background Antibody–drug conjugates have emerged as a powerful strategy in cancer therapy and combine the ability of monoclonal antibodies to specifically target tumour cells with the highly potent killing activity of drugs with payloads too toxic for systemic administration. Trastuzumab deruxtecan (also known as DS-8201) is an antibody–drug conjugate comprised of a humanised antibody against HER2, a novel enzyme-cleavable linker, and a topoisomerase I inhibitor payload. We assessed its ...
110 CitationsSource
#1Naoki Takegawa (Kindai University)H-Index: 10
#2Yoshikane Nonagase (Kindai University)H-Index: 8
Last. Junji Tsurutani (Kindai University)H-Index: 33
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Anti-HER2 therapies are beneficial for patients with HER2-positive breast or gastric cancer. T-DM1 is a HER2-targeting antibody-drug conjugate (ADC) comprising the antibody trastuzumab, a linker, and the tubulin inhibitor DM1. Although effective in treating advanced breast cancer, all patients eventually develop T-DM1 resistance. DS-8201a is a new ADC incorporating an anti-HER2 antibody, a newly developed, enzymatically cleavable peptide linker, and a novel, potent, exatecan-derivative topoisome...
52 CitationsSource
#1Suguru Ueno (Daiichi Sankyo)H-Index: 4
#2Kenji Hirotani (Daiichi Sankyo)H-Index: 10
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 14 authors...
Background HER3 (human epidermal growth factor receptor 3) is a member of HER family, and overexpressed in breast cancer, NSCLC, melanoma, gastric cancer and pancreatic cancer patients` tissues. U3-1402a is an antibody-drug conjugate (ADC) comprised of a fully human anti-HER3 monoclonal immunoglobulin G1 (IgG1) antibody (U3-1287) covalently conjugated via a cleavable peptide linker to exatecan derivative (DXd). The DXd is released after internalization of U3-1402a and leads to apoptosis of the t...
1 CitationsSource
#1Yoshikane Nonagase (Kindai University)H-Index: 8
#2Naoki Takegawa (Kindai University)H-Index: 10
Last. Kazuhiko Nakagawa (Kindai University)H-Index: 98
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Background Anti-HER2 therapies are beneficial for patients with HER2-positive breast and gastric cancer. T-DM1 is an HER2-targeting antibody-drug conjugate (ADC), which is structurally composed of the anti-HER2 antibody trastuzumab and the tubulin inhibitor DM1. T-DM1 has shown efficacy in patients with advanced breast cancer, but all patients eventually develop resistance to T-DM1. DS-8201a is a novel ADC composed of an anti-HER2 antibody and a novel potent topoisomerase I inhibitor DX-8951 der...
1 CitationsSource
#1Tomomi Nakayama Iwata (Daiichi Sankyo)H-Index: 3
#2Chiaki Ishii (Daiichi Sankyo)H-Index: 3
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 5 authors...
1031Background: DS-8201a, a HER2-targeting antibody–drug conjugate (ADC), with a topoisomerase I inhibitor, exatecan drivative (DX-8951 derivative, DXd) has been shown to have antitumor effects in preclinical xenograft models and clinical trials, but the involvement of the immune system in the antitumor efficacy of DS-8201a has not been elucidated yet. Methods: The antitumor efficacy of DS-8201a individually and in combination with an anti-PD-1 antibody was determined in a syngeneic mouse model ...
5 CitationsSource