A5006003927- Radiopharmaceutical Chemistry and Applications
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Boron Compounds in Chemistry
- Medical Imaging Techniques and Applications
- CAR-T cell therapy research
- Nanoparticle-Based Drug Delivery
- Cancer, Hypoxia, and Metabolism
- Growth Hormone and Insulin-like Growth Factors
- Radiomics and Machine Learning in Medical Imaging
- Amino Acid Enzymes and Metabolism
- PARP inhibition in cancer therapy
- Cancer Cells and Metastasis
- Orthopedic Infections and Treatments
- Cancer-related Molecular Pathways
- Biosimilars and Bioanalytical Methods
- Glycosylation and Glycoproteins Research
- Neuropeptides and Animal Physiology
- Medical Imaging and Pathology Studies
- Glioma Diagnosis and Treatment
- Axon Guidance and Neuronal Signaling
- Nanoplatforms for cancer theranostics
- Synthesis and Biological Evaluation
- Metabolism, Diabetes, and Cancer
AstraZeneca (United States)
2019-2021
AstraZeneca (United Kingdom)
2011
Vanderbilt University
1989-1996
Beth Israel Deaconess Hospital
1989
S100 beta produced in Escherichia coli from a synthetic gene (Van Eldik, L. J., J. Staecker, and F. Winningham-Major. 1988. Biol. Chem. 263:7830-7837) stimulates neurite outgrowth enhances cell maintenance cultures of embryonic chick cerebral cortex neurons. In control experiments, the extension activity is reduced by preincubation with antibodies made against bovine brain beta. When either two cysteines are altered site-directed mutagenesis, resultant proteins maintain overall biochemical...
Abstract The EphA2 receptor tyrosine kinase is selectively expressed on the surface of many different human tumors. We have previously shown that tumor cells can be targeted by monoclonal antibodies and these function, in part, inducing internalization degradation. In this report, we describe isolation characterization a fully antibody (1C1) binds both rodent receptor. After cell binding, induces rapid phosphorylation, internalization, degradation Because bind internalize provide vehicle for...
Insulin-like growth factors (IGF), IGF-I and IGF-II, are small polypeptides involved in regulating cell proliferation, survival, differentiation, transformation. IGF activities mediated through binding activation of IGF-1R or insulin receptor isoform A (IR-A). The role the pathway promoting tumor survival is well documented. Overexpression IGF-II IR-A reported multiple types cancer proposed as a potential mechanism for cells to develop resistance IGF-1R-targeting therapy. MEDI-573 fully...
We tested the effects of neutral metalloendopeptidase (NEP) inhibitor, thiorphan (0.17, 0.5, and 1.7 mg i.v), angiotensin-converting enzyme (ACE) captopril (0.5, 1.7, 5.0 i.v.), on bronchoconstrictor response to rapid intravenous infusions substance P (0.1 30 nmol/kg) in anesthetized, mechanically ventilated guinea pigs. The decreases pulmonary conductance dynamic compliance caused by were greater animals treated with either or than control animals. Thiorphan (0.5 mg) had no effect airway...
Immunoglobulin E (IgE) plays a key role in allergic asthma and is clinically validated target for monoclonal antibodies. Therapeutic anti-IgE antibodies block the interaction between IgE Fc epsilon (Fcε) receptor, which eliminates or minimizes phenotype but does not typically curtail ongoing production of by B cells. We generated high-affinity (MEDI4212) that have potential to both neutralize soluble eliminate IgE-expressing B-cells through antibody-dependent cell-mediated cytotoxicity....
Humans and higher primates are unique in that they lack uricase, the enzyme capable of oxidizing uric acid. As a consequence this deficiency, humans have high serum acid levels. In some people, levels rise above solubility limit resulting crystallization joints, acute inflammation response to those crystals causes severe pain; condition known as gout. Treatment for gout includes injection non-human uricase reduce Krystexxa® is hyper-PEGylated pig-baboon chimeric indicated chronic refractory...
Abstract Purpose: Platinum and PARP inhibitors (PARPi) demonstrate activity in breast ovarian cancers, but drug resistance ultimately emerges. Here, we examine B7-H4 expression primary recurrent high-grade serous carcinoma (HGSOC) the of a B7-H4-directed antibody–drug conjugate (B7-H4-ADC), using pyrrolobenzodiazepine-dimer payload, PARPi- platinum-resistant HGSOC patient-derived xenograft (PDX) models. Experimental Design: was quantified by flow cytometry IHC. B7-H4-ADC efficacy tested...
EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in variety of human tumor types. Previous studies demonstrated agonist monoclonal antibodies targeting induced the internalization and degradation receptor, thereby abolishing its oncogenic effects. In this study, vitro vivo antibody-dependent cell-mediated cytotoxicity (ADCC) activity effector-enhanced was evaluated. With cell lines healthy peripheral blood monocytes, approximately 80% killing. dose-dependent...
MEDI-565 (also known as MT111) is a bispecific T-cell engager (BiTE®) antibody in development for the treatment of patients with cancers expressing carcinoembryonic antigen (CEA). binds CEA on cancer cells and CD3 T to induce mediated killing cells. To understand molecular basis human recognition by how polymorphisms spliced forms may affect activity, we mapped epitope using mutagenesis homology modeling approaches. We found that recognized conformational A2 domain comprised amino acids...
It has been hypothesized that the neutrophil chemoattractant interleukin‐8 (IL‐8) forms a gradient in oral cavity, with highest concentration of IL‐8 produced closest to bacterial biofilm. In periodontitis, this is disrupted, impairing chemotaxis diseased sites. Treponema denticola prominently associated periodontal disease, yet little known about its ability modulate production inflammatory mediators by epithelial cells. Others have shown dentilisin, major outer membrane protease T. ,...
The annual European Antibody Congress (EAC) has traditionally been the key event for updates on critical scientific advances in antibody field, and 2013 was no exception. Organized by Terrapinn, well-attended meeting featured presentations considerations developing antibodies antibody-like therapeutics, with separate tracks antibody-drug conjugates, naked antibodies, multispecific or protein scaffolds. overall focus of EAC current approaches to enhance functionality therapeutic other...
The biologic activity of substance P has been demonstrated to be limited both in vivo and vitro by a membrane-bound protease, neutral endopeptidase (EC 3.4.24.11). interaction with its receptor on guinea pig lung tissues was studied the presence an inhibitor under conditions that protect peptide from degradation. Uptake 0.1 nM [125I]-BH-substance membrane preparations rapid at 4° C, reaching equilibrium 30 40 min, binding stable for least min thereafter. Binding reversible saturable....
Abstract Antibody drug conjugates (ADCs) combine the specificity of antibodies with potent cytotoxicity small molecule drugs and have shown to provide therapeutic options for various cancers. We report herein discovery a HER2-targeting ADC MEDI4276 that showed cell killing activity in vitro cancer lines express HER2 receptor. The observed translated into vivo tumor growth inhibition xenograft mouse models. is homogeneous precise control loading following site specific conjugation cytotoxic...
Abstract MEDI7247 is a first in class ADC consisting of human anti-ASCT2 monoclonal antibody site specifically conjugated to DNA cross-linking pyrrolobenzodiazepine (PBD) dimers. ASCT2 (SLC1A5) multi-pass, Na+-dependent neutral amino acid transporter that mediates the uptake acids required for tumor growth and progression. highly overexpressed many hematologic cancers, most notably Multiple Myeloma (MM - 100% positive), Acute Myeloid Leukemia (AML positive) Diffuse Large B cell lymphoma...
Abstract MEDI7247 is a first in class ADC consisting of human anti-ASCT2 monoclonal antibody, site specifically conjugated to highly cytotoxic DNA cross-linking pyrrolobenzodiazepine (PBD) dimers (DAR 2) via protease-cleavable linker. ASCT2 (SLC1A5) multi-pass, Na+-dependent, neutral amino acid transporter that mediates the uptake acids required for tumor growth and progression. over-expression has been identified on numerous solid indications including pancreatic (94% Positive), small cell...
Abstract Platelet‐derived growth factor (PDGF) stimulates the expression of a number genes associated with entry quiescent Balb/c‐3T3 fibroblasts into cell cycle. We determined that two these genes, c‐ myc and fos , are induced equivalently in medium supplemented platelet‐poor plasma (PPP) either PDGF‐BB or PDGF‐AA. The rate at which entered S phase was also similar PDGF‐BB– AA–treated cells as late G 1 gene, thymidine kinase (TK). However, PDGF‐AA must be present for period 16 h to...
<p>Immunohistochemical analysis of PDX tumors for Ki67 after ADC treatment.</p>
<p>Individual mouse data and statistical analysis of WO-2 PDX in vivo study.</p>