A5077111567- Nerve injury and regeneration
- Monoclonal and Polyclonal Antibodies Research
- Neuropeptides and Animal Physiology
- Retinal Development and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Pain Mechanisms and Treatments
- Glycosylation and Glycoproteins Research
- HER2/EGFR in Cancer Research
- Biosimilars and Bioanalytical Methods
- Hepatitis B Virus Studies
- Biochemical and Structural Characterization
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Protein Degradation and Inhibitors
- T-cell and B-cell Immunology
- Transgenic Plants and Applications
- RNA Interference and Gene Delivery
- Botulinum Toxin and Related Neurological Disorders
- Protein purification and stability
- Herpesvirus Infections and Treatments
- Cell death mechanisms and regulation
- MicroRNA in disease regulation
- Nuclear Receptors and Signaling
- Tendon Structure and Treatment
- Rheology and Fluid Dynamics Studies
Merck & Co., Inc., Rahway, NJ, USA (United States)
1990-2022
Palo Alto Institute
2015
Seagen (United States)
2006-2015
Sanofi (France)
2015
Bristol-Myers Squibb (United States)
2015
Eli Lilly (United States)
2015
AbbVie (United States)
2015
Biogen (United States)
2015
Amgen (United States)
2015
Novartis (Switzerland)
2015
Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and pathological processes such as tumor growth, rheumatoid arthritis, ocular neovascularization. A recombinant humanized monoclonal antibody (rhuMAb), rhuMAb VEGF, has been developed to inhibit the effects of VEGF treatment solid tumors. Intravenous s.c. pharmacokinetic studies were conducted mice, rats, cynomolgus monkeys. In addition, tissue distribution i.v. 125I-rhuMAb was investigated rabbits. At dose...
Cell division, cell death, and remodeling of connections are major features the construction mammalian CNS. We have begun to address role neurotrophins in these events through characterization expression their receptors developing ferret visual system. By use chemical cross-linking iodinated neurotrophins, proteins corresponding trkB, trkC, p75 were identified as for brain-derived neurotrophic factor (BDNF) neurotrophin-3 (NT-3) throughout development. BDNF was also cross-linked a truncated...
Members of the NGF family proteins act as neurotrophic agents for defined populations peripheral and central neurons during embryonic postnatal development. We have studied presence receptors brain-derived factor (BDNF) neurotrophin-3 - 4/5 (NT-3, NT-4/5) by cross-linking radioiodinated neurotrophins to specific cell surface receptors. identified neurotrophin representing full-length TrkB TrkC their truncated forms (lacking a functional cytoplasmic kinase domain) in neuronal well...
The MYC oncogene is upregulated in human cancers by translocation, amplification, and mutation of cellular pathways that regulate Myc. Myc/Max heterodimers bind to E box sequences the promoter regions genes activate transcription. inhibitor Omomyc can reduce ability specific promoters target binding directly as demonstrated chromatin immunoprecipitation (CHIP). Here, we demonstrate both a proximity ligation assay (PLA) double (ReCHIP) preferentially binds Max, not Myc, mediate inhibition...
Apo2L/TRAIL [Apo2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand], a member of the TNF cytokine superfamily, induces cell death by apoptosis in number human cancer cells and is potential agent for therapy. We have characterized vitro stability serum tissue distribution metabolism xenograft model colon carcinoma (COLO205). was stable after incubation serum, with no significant high molecular weight complexes or degradation products observed. After i.v. administration...
Abstract The expression of neurotrophin (NGF, BDNF, and NT‐3) mRNAs in 24 cell lines derived from human malignant gliomas was studied by Northern analysis. Widespread genes found with BDNF being the most abundantly expressed. Nearly all expressed about two‐thirds NGF NT‐3. Half analyzed three neurotrophins. Secretion into medium several could be detected ELISA a PC12 neurite outgrowth assay. Immuno‐ bioactive isolated conditioned one line. No evidence receptors trk B analysis found. Receptor...
Abstract Neurotrophic factors regulate the developmental survival and differentiation of specific neuronal populations. Brain‐derived neurotrophic factor (BDNF) neurotrophin‐3 (NT‐3) are members nerve growth (NGF) protein family, also known as neurotrophins. Insights into different roles neurotrophins can be gained by studying expression their functional receptors. Here we report development procedures for radiolabeling efficient crosslinking to cell‐surface BDNF NT‐3 receptors in cell lines...
CC49 is a clinically validated antibody with specificity for TAG-72, carbohydrate epitope that overexpressed and exposed on the cell surface in large fraction of solid malignancies. We constructed single-chain fragment (scFv) based fused it to beta-lactamase (BLA). Following optimization scFv domain by combinatorial consensus mutagenesis (CCM) increased expression stability, we characterized protein variant binding, vivo pharmacokinetics (PK), antitumor efficacy. The fusion TAB2.5 possessed...
Interleukin 10 (IL-10) is a potent cytokine homodimer with multiple immunoregulatory functions. Here, we have characterized the effects of PEGylation and formation human IL-10 (hIL-10)/humanized anti-human (hαhIL-10) immune complexes in pharmacokinetics, biodistribution, biotransformation mice. To assess fate native, PEGylated, antibody-bound IL-10; implemented an analytical set fluorescence emission-linked assays. Plasma size exclusion chromatography analysis indicated that fluoro-labeled...
Peripheral neuropathy is a significant complication of diabetes resulting in increased patient morbidity and mortality. Deficiencies neurotrophic substances (e.g. NGF, NT-3, IGF-I) have been proposed as pathogenetic mechanisms the development distal symmetrical sensory diabetic polyneuropathy, salutary effects exogenous NGF administration reported animal models. In comparison, relatively little known concerning effect on experimental sympathetic autonomic neuropathy. We developed an model...
Administration of biologics to enhance T-cell function is part a rapidly growing field cancer immunotherapy demonstrated by the unprecedented clinical success several immunoregulatory receptor targeting antibodies. While these biologic agents confer significant anti-tumor activity through targeted immune response modulation, they can also elicit broad responses potentially including production anti-drug antibodies (ADAs). DTA-1, an agonist monoclonal antibody against GITR, highly effective...
In order to study regulation of the nerve growth factor (NGF) receptor during embryogenesis in chick brain, we have used affinity crosslinking tissues with 125I-NGF. NGF interacts high- and low-affinity receptors; high-affinity receptors are required for majority NGF's actions. Most measurements levels do not distinguish between forms receptor. We lipophilic agent HSAB identify high-affinity, functional development chicken central nervous system. A peak expression Embryonic Days 5–10 was...
In this study, we have characterized the metabolism, tissue disposition, excretion routes, and plasma pharmacokinetics of recombinant human nerve growth factor after single multiple s.c. administration in male cynomolgus monkeys. Unlabeled (NGF; 2 mg/kg) was administered three times a week for 4 weeks full pharmacokinetic profile obtained doses 1 12. For distribution studies, 0.8 microg/kg trace (125)I-labeled dosed. Histological analysis emulsion-microautoradiography indicated that specific...
The purpose of this investigation was to characterize the stability, activity, and interactions recombinant human nerve growth factor (rhNGF) in various biological matrices vitro vivo. rhNGF (10 microg/ml) remained stable plasma for up 4 days at 37 degrees C. There a decrease recovery after incubation lower concentrations (20 ng/ml) longer time periods (3 5 C). Size exclusion HPLC analysis indicated that forms high molecular weight (HMW) complexes long periods. We confirmed...