A5035406837- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Chemical Reactions and Isotopes
- Endometriosis Research and Treatment
- Gastrointestinal Tumor Research and Treatment
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Ovarian cancer diagnosis and treatment
- Radiopharmaceutical Chemistry and Applications
- Gastric Cancer Management and Outcomes
- CAR-T cell therapy research
- Synthesis and Biological Evaluation
- Cancer Treatment and Pharmacology
- Protein purification and stability
- Neuroblastoma Research and Treatments
- Multiple Myeloma Research and Treatments
- Estrogen and related hormone effects
- Peptidase Inhibition and Analysis
- Sarcoma Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- Inflammatory Myopathies and Dermatomyositis
- Bioactive Compounds and Antitumor Agents
- Systemic Sclerosis and Related Diseases
- Web Applications and Data Management
Daiichi Sankyo (Germany)
2009-2025
Daiichi-Sankyo (South Korea)
2025
Daiichi-Sankyo (Japan)
2016-2024
Tokyo Women's Medical University
2018-2024
University College London
2010-2011
Sendai National College of Technology
2010
An anti-HER2 antibody-drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as new antitumor drug candidate, and its preclinical pharmacologic profile assessed.In vitro in vivo activities of DS-8201a were evaluated compared T-DM1 several HER2-positive cell lines patient-derived xenograft (PDX) models. The mechanism action for the efficacy also evaluated. Pharmacokinetics cynomolgus monkeys safety profiles rats assessed.DS-8201a exhibited HER2 expression-dependent...
Abstract Purpose: HER3 is a compelling target for cancer treatment; however, no HER3-targeted therapy currently clinically available. Here, we produced U3-1402, an anti-HER3 antibody–drug conjugate with topoisomerase I inhibitor exatecan derivative (DXd), and systematically investigated its targeted drug delivery potential antitumor activity in preclinical models. Experimental Design: In vitro pharmacologic activities the mechanisms of action U3-1402 were assessed several human cell lines....
Abstract 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), a potent DNA topoisomerase I inhibitor (DXd), evaluated its antitumor activity safety profiles in preclinical models. The pharmacologic mechanism of action Dato-DXd were investigated several human cancer lines xenograft mouse models including...
B7-H3 is overexpressed in various solid tumors and has been considered as an attractive target for cancer therapy. Here, we report the development of DS-7300a, a novel B7-H3-targeting antibody-drug conjugate with potent DNA topoisomerase I inhibitor, its vitro profile, pharmacokinetic profiles, safety vivo antitumor activities nonclinical species. The specificity species cross-reactivity DS-7300a were assessed. Its pharmacologic evaluated several human cell lines xenograft mouse models,...
Abstract Cadherin-6 (CDH6) is expressed in several cancer types, but no CDH6-targeted therapy currently clinically available. Here, we generated raludotatug deruxtecan (R-DXd; DS-6000), a novel CDH6-targeting antibody–drug conjugate with potent DNA topoisomerase I inhibitor, and evaluated its properties, pharmacologic activities, safety profile. In vitro activities the mechanisms of action R-DXd were assessed serous-type ovarian renal cell carcinoma lines. vivo human lines patient-derived...
Mixed lineage leukemia 1-rearranged (MLL1-r) acute patients respond poorly to currently available treatments and there is a need develop more effective therapies directly disrupting the Menin‒MLL1 complex. Small-molecule-mediated inhibition of protein‒protein interaction between Menin MLL1 fusion proteins potential therapeutic strategy for with MLL1-r or mutated-nucleophosmin 1 (NPM1c) leukemia. In this study, we preclinically evaluated new compound DS-1594a its salts.We preclinical efficacy...
Currently, the only approved treatments for gastrointestinal stromal tumor (GIST) are tyrosine kinase inhibitors (TKI), 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-tyrosine target GIST, developed new GPR20 IHC, assessed expression cell lines, patient-derived xenografts, clinical samples from two institutes (United States Japan). We studied stratified...
Of the four human IgG antibody subclasses IgG1–IgG4, IgG4 is of interest in that it does not activate complement and exhibits atypical self-association, including formation bispecific antibodies. The solution structures antibodies are critical to understand function therapeutic applications. Thus was studied by synchrotron X-ray scattering. Guinier radius gyration RG increased from 5.0 nm 5.1 with an increase concentration. distance distribution P(r) revealed a single peak at 0.3 mg/ml,...
l ‐Type amino acid transporter 1 ( LAT 1) disulfide linked to CD 98 heavy chain (hc) is highly expressed in most cancer cells, but weakly normal cells. In the present study, we developed novel anti‐ mA bs and showed internalization activity, inhibitory effects of uptake cell growth antibody‐dependent cellular cytotoxicity, as well vivo antitumor athymic mice. Furthermore, examined reactivity with Macaca fascicularis evaluate possible side‐effects antihuman clinical trials. Antihuman reacted...
e24206 Background: DS-1062a is a trophoblast cell surface protein 2 (TROP2)-targeting antibody-drug conjugate (ADC) comprised of humanized anti-TROP2 monoclonal antibody, enzymatically cleavable peptide-linker, and novel topoisomerase I inhibitor DXd which derivative Exatecan (DX-8951). TROP2 36-kDa single-pass transmembrane overexpressed in various epithelial tumors including non-small lung cancer (NSCLC) with relatively low restricted expression normal tissues, associated aggressive tumor...
<div>Abstract<p>Cadherin-6 (CDH6) is expressed in several cancer types, but no CDH6-targeted therapy currently clinically available. Here, we generated raludotatug deruxtecan (R-DXd; DS-6000), a novel CDH6-targeting antibody–drug conjugate with potent DNA topoisomerase I inhibitor, and evaluated its properties, pharmacologic activities, safety profile. <i>In vitro</i> activities the mechanisms of action R-DXd were assessed serous-type ovarian renal cell carcinoma...
Abstract Background: Tumor-associated mucin-1 (TA-MUC1) is a tumor-specific transmembrane glycoprotein with aberrant glycosylation. It highly expressed in various human epithelial cancers, making it an attractive target for cancer therapy. DS-3939a TA-MUC1 targeting antibody-drug conjugate (ADC) structurally composed of humanized anti-TA-MUC1 antibody, enzymatically cleavable tetrapeptide-based linker, and DNA topoisomerase I inhibitor (DXd) high drug-to-antibody ratio (DAR). In this study,...
The number of Web applications handling online transaction is increasing, but verification the correctness application design has been done manually. This paper proposes a method for modeling using two finite-state automata, i.e., page automaton which specifies transitions, and an internal state transitions application. An example modeled by proposed checked model checker Spin.
Abstract Background HER3 (human epidermal growth factor receptor 3) is a member of HER family, and overexpressed in breast cancer, NSCLC, melanoma, gastric cancer pancreatic patients` tissues. U3-1402a an antibody-drug conjugate (ADC) comprised fully human anti-HER3 monoclonal immunoglobulin G1 (IgG1) antibody (U3-1287) covalently conjugated via cleavable peptide linker to exatecan derivative (DXd). The DXd released after internalization leads apoptosis the target tumor cells by inhibition...
Abstract More than 85% of GISTs are driven by activating mutations in KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor alpha (PDGFRA). Currently, the only approved treatments for GIST directed inhibitors (TKIs). However, treatment with TKIs eventually results disease progression most often due to development secondary resistance KIT. In addition, these agents have limited activity PDGFRA mutant and KIT/PDGFRA wild type (WT) as primary therapy. Therefore, it...
IL(interleukin)-18 is known to induce proliferation of Vδ2+ T cells and expression CD56, resulting in enhancement cytotoxic activity. We focused on the CD56 direct action IL-18 evaluate importance for developing cells-based adoptive immunotherapy. Peripheral blood mononuclear (PBMCs) were purified from heparinized healthy donors cancer patients. CD56− isolated subjects cultured with IL-2 or alone. The number increased compared those However, this increase was not statistically significant....