A5068006242- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Advanced Breast Cancer Therapies
- Cell Adhesion Molecules Research
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Treatments and Mutations
- Cancer Research and Treatments
- Bladder and Urothelial Cancer Treatments
- Asthma and respiratory diseases
- Cancer Treatment and Pharmacology
- Urinary and Genital Oncology Studies
- Immunotherapy and Immune Responses
- Breast Cancer Treatment Studies
- Melanoma and MAPK Pathways
- Parathyroid Disorders and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Immune Response and Inflammation
- Advanced Biosensing Techniques and Applications
- Magnesium in Health and Disease
- Click Chemistry and Applications
- Ion Channels and Receptors
- Ion channel regulation and function
Pfizer (United States)
2024
Seagen (United States)
2020-2023
Amgen (United States)
2007-2020
University of California, San Francisco
2016
EKOS Corporation
1999-2000
There is an unmet need in severe asthma where approximately 40% of patients exhibit poor beta-agonist responsiveness, suffer daily symptoms and show frequent exacerbations. Antagonists the Ca2+-activated-Cl¯ channel, TMEM16A, offers a new mechanism to bronchodilate airways block multiple contractiles operating disease. To identify TMEM16A antagonists we screened library ~580,000 compounds. The anthelmintics niclosamide, nitazoxanide related compounds were identified as potent that blocked...
Abstract CD11c, a member of the leukointegrin family, is expressed prominently on tissue macrophages and dendritic cells binds to complement fragment (iC3b), provisional matrix molecules (fibrinogen), Ig superfamily cell adhesion molecule, ICAM-1. CD11c has been proposed function in phagocytosis, migration, cytokine production by monocytes/macrophages as well induction T proliferation Langerhans cells. Using assays quantify CD11c-mediated adhesion, we demonstrate that recognizes ICAM-2...
SGN-B7H4V is a novel investigational vedotin antibody-drug conjugate (ADC) comprising B7-H4-directed human monoclonal antibody conjugated to the cytotoxic payload monomethyl auristatin E (MMAE) via protease-cleavable maleimidocaproyl valine citrulline (mc-vc) linker. This linker-payload system has been clinically validated in multiple Food and Drug Administration approved agents including brentuximab vedotin, enfortumab tisotumab vedotin. B7-H4 an immune checkpoint ligand with elevated...
SGN-CD228A is an investigational antibody-drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. consists of humanized antibody, hL49, with high specificity and affinity for CD228 that stably conjugated 8 molecules the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via novel glucuronide linker. We performed comprehensive IHC studies, which corroborated published RNA sequencing data...
Etelcalcetide, a novel peptide agonist of the calcium-sensing receptor, prevents vascular calcification in rat model renal insufficiency with secondary hyperparathyroidism. Vascular occurs frequently patients chronic kidney disease (CKD) and is consequence impaired mineral homeostasis hyperparathyroidism (SHPT). Etelcalcetide substantially lowers parathyroid hormone (PTH) fibroblast growth factor-23 (FGF23) levels SHPT on hemodialysis. This study compared effects etelcalcetide paricalcitol...
We developed selective monoclonal antibodies and used them for Western immunocytochemical analyses to determine the tissue cellular distribution of human cyclic GMP-stimulated phosphodiesterase (PDE2). analysis revealed PDE2A expression in a variety types, including cerebellum, neocortex, heart, kidney, lung, pulmonary artery, skeletal muscle. Immunocytochemical subset endothelial cells. immunostaining was detected venous capillary cells cardiac renal but not arterial These results were...
AMG X, a human neutralizing monoclonal antibody (mAb) against soluble protein, caused thrombocytopenia, platelet activation, reduced mean arterial pressure, and transient loss of consciousness in cynomolgus monkeys after first intravenous administration. In vitro, X induced activation platelets from macaque species but not humans or baboons. Other similar mAbs the same pharmacological target failed to induce these vivo vitro effects. addition, protein was known be expressed on platelets,...
Abstract The antibody-drug conjugate enfortumab vedotin (EV; AGS22C3E) targets Nectin-4 expressing tumor cells by delivering MMAE, a potent microtubule disrupting agent, to induce cell death. EV has demonstrated single agent activity and encouraging (71% ORR) when combined with pembrolizumab (anti-PD-1) in the 1L setting of cis-ineligible metastatic urothelial carcinoma (mUC) (EV-103, NCT03288545). Here we that may promote multiple mechanisms action including bystander killing hallmarks...
Sustained elevation of parathyroid hormone (PTH) is catabolic to cortical bone, as evidenced by deterioration in bone structure (cortical porosity), and a major factor for increased fracture risk chronic kidney disease (CKD). Etelcalcetide (AMG 416), novel peptide agonist the calcium-sensing receptor, reduces PTH levels subtotal nephrectomized (Nx) rats hemodialysis patients with secondary hyperparathyroidism (SHPT) clinical studies; however, effects etelcalcetide on have not been...
<h3>Background</h3> Enfortumab vedotin (EV) is a first-in-class Nectin-4-directed antibody-drug conjugate (ADC) with demonstrated improved overall survival in patients previously treated advanced-stage urothelial carcinoma.<sup>1</sup> EV comprised of fully human monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) by protease cleavable maleimidocaproyl-valine-citrulline linker. has multifaceted mechanism action. Previously, we that induces...
To further understand the role of pituitary adenylate cyclase-activating polypeptide 1 (PAC1) receptors in headache disorders, we mapped their expression tissues trigemino-autonomic system by immunohistochemistry and situ hybridization.To optimize screening for monoclonal antibodies suitable on formalin-fixed, paraffin-embedded tissues, developed a new enzyme-linked immunosorbent assay using cells overexpressing human PAC1 receptors. 169G4.1 was selected from these studies analysis rat...
The oncogenic receptor HER2 is overexpressed in many cancers, including up to 20% of breast cancers. Despite the availability HER2-targeted treatments, patients’ disease often progresses during therapy, underscoring need for novel treatment strategies. addition tucatinib, a reversible, highly selective tyrosine kinase inhibitor (TKI), with trastuzumab and capecitabine significantly improved survival outcomes patients HER2-positive metastatic cancer, those active brain metastases. We...
Abstract Feline McDonough Sarcoma-like tyrosine kinase 3 (FLT3), a tyrosine-protein involved in hematopoiesis, is detectable on the cell surface of approximately 80% leukemia isolates from adult patients with acute myeloid (AML). AMG 553 an investigational chimeric antigen receptor (CAR) T-cell immunotherapy for treatment AML. FLT3 expression analysis and vitro vivo studies were leveraged to evaluate nonclinical safety 553. Cynomolgus monkeys administered autologous anti-FLT3 CAR T cells...
<h3>Background</h3> Tisotumab vedotin (TV) is an investigational antibody-drug conjugate composed of a tissue factor (TF)-directed human monoclonal antibody covalently linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via protease-cleavable linker. TV demonstrated single activity (24% objective response rate [ORR]) in previously treated recurrent or metastatic cervical cancer (NCT03438396) where currently, there no standard care and ORRs are typically less than 15%...
<h3>Background</h3> SGN-B7H4V is a novel, investigational vedotin antibody drug conjugate (ADC) directed to B7-H4, member of the B7 family immune checkpoint ligands. B7-H4 expression elevated on variety solid tumors including breast, ovarian, and endometrial tumors.<sup>1</sup> composed fully human IgG1 anti-B7-H4 monoclonal (mAb) conjugated microtubule disrupting agent monomethyl auristatin E (MMAE) via protease-cleavable peptide linker. designed bind internalize ligand B7-H4/ADC complex...
Abstract Enfortumab vedotin (EV) is a monomethyl auristatin E (MMAE) containing antibody-drug conjugate directed to Nectin-4, which highly expressed in bladder cancers. Preclinically, EV has demonstrated tumor cell-killing by direct cytotoxicity, bystander toxicity, and induction of the hallmarks immunogenic cell death. In EV-301, phase 3 clinical study, monotherapy showed an overall survival (OS) benefit vs chemotherapy patients with locally advanced or metastatic urothelial carcinoma...
Abstract Mast cells play an important role in allergic inflammation. Upon activation by cross-linking of FcεRI, they rapidly release granule-associated chemical mediators and secrete cytokines, fatty acids lipids which mediate GPR34 is a GPCR expressed on mast has been proposed to be receptor for lysophosphatidylserine (lysoPS), phospholipid derivative can potentiate antigen-induced cell degranulation (BBRC 341: 1078, 2006). To determine if involved response, we generated GPR34-/- mice...
Abstract SGN-B6A is a novel investigational antibody-drug conjugate (ADC) directed to integrin beta-6 and uses the clinically validated vedotin drug-linker platform that delivers microtubule disrupting agent, monomethyl auristatin E (MMAE). designed bind internalize beta-6/ADC complex from surface of malignant cells release cytotoxic payload MMAE. We have previously demonstrated antitumor activity in cell line-derived xenograft models originating multiple carcinomas as well patient-derived...
Abstract Monomethyl auristatin E (MMAE), the payload delivered by vedotin ADCs, exerts its cytotoxic effects via microtubule disruption and induction of ER stress, leading to apoptosis tumor cell death. In addition, MMAE also has ability induce immunogenic death (ICD) immune modulation in microenvironment (TME) (Liu, 2020; Gray, 2020). Other clinical-stage approved ADCs incorporate payloads that cause (DM1, DM4), or drive DNA damage through topoisomerase I inhibition (exatecan) as primary...
<h3>Background</h3> Sigvotatug vedotin (SV, formerly SGN-B6A) is an antibody-drug conjugate (ADC) comprised of the antibody, h2A2, which binds to integrin-β6 (IB6). IB6 exclusively integrin-αv and functions as heterodimer αvβ6. SV conjugated clinically validated payload monomethyl auristatin E (MMAE). Beyond its role in driving tumor intrinsic pathways oncogenesis invasiveness, αvβ6 regulates activation latent transforming growth factor-β (TGFβ) by binding latency associated protein (LAP)...
There is an unmet need in severe asthma where approximately 40% of patients exhibit poor β-agonist responsiveness, suffer daily symptoms and show frequent exacerbations. Antagonists the Ca 2+ -activated-Cl − channel, TMEM16A, offers a new mechanism to bronchodilate airways block multiple contractiles operating disease. To identify TMEM16A antagonists we screened library ~580,000 compounds. The anthelmintics niclosamide, nitazoxanide related compounds were identified as potent that blocked...
7032 Background: FMS-like tyrosine kinase 3 (FLT3) is a tyrosine-protein involved in hematopoiesis. In acute myeloid leukemia (AML), higher FLT3 transcript levels, independent of the presence mutations, correlate with leukocyte counts and degrees bone marrow infiltration by leukemic cells. protein detectable on cell surface more than 80% isolates from adult AML patients whereas mutations are present only approximately one third patients. AMG 553 novel, investigational, adoptive cellular...
Abstract Tucatinib is an investigational, oral, small molecule tyrosine kinase inhibitor that highly selective for the domain of HER2, without significant inhibition EGFR. Recently, HER2CLIMB (NCT02614794), a pivotal, randomized, international, double-blind trial evaluated tucatinib or placebo in combination with trastuzumab and capecitabine patients HER2+ metastatic breast cancer (MBC) brain metastases, after progression trastuzumab, pertuzumab, ado-trastuzumab emtansine (T-DM1), showed...