A5049321550- Lung Cancer Treatments and Mutations
- Herpesvirus Infections and Treatments
- HER2/EGFR in Cancer Research
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- Angiogenesis and VEGF in Cancer
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- Colorectal Cancer Treatments and Studies
- MicroRNA in disease regulation
- Cell Adhesion Molecules Research
- HIV Research and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Reproductive System and Pregnancy
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Neuropeptides and Animal Physiology
- SARS-CoV-2 and COVID-19 Research
- T-cell and Retrovirus Studies
- Receptor Mechanisms and Signaling
- Kruppel-like factors research
- Estrogen and related hormone effects
- Computational Drug Discovery Methods
- Cancer Treatment and Pharmacology
Regeneron (United States)
2014-2023
Pearl River Community College
1997-2004
Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola-one from genetically humanized mice and the other a human survivor. Here, we describe parallel efforts using both convalescent patients to generate against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, which large collection of fully that were characterized binding, neutralization,...
Mice genetically engineered to be humanized for their Ig genes allow human antibody responses within a mouse background (HumAb mice), providing valuable platform the generation of fully therapeutic antibodies. Unfortunately, existing HumAb mice do not have functional immune systems, perhaps because manner in which genetic humanization was carried out. Heretofore, been generated by disrupting endogenous and simultaneously introducing transgenes at different random location; KO-plus-transgenic...
Traditional approaches to antimicrobial drug development are poorly suited combatting the emergence of novel pathogens. Additionally, lack small animal models for these infections hinders in vivo testing potential therapeutics. Here we demonstrate use VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside VelociGene (which allows rapid engineering genome) quickly develop evaluate antibodies against an emerging viral disease....
For most classes of drugs, rapid development therapeutics to treat emerging infections is challenged by the timelines needed identify compounds with desired efficacy, safety, and pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method overcome many these hurdles rapidly produce for diseases. In this study, we deployed a platform generate, test, develop fully Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) immunizing VelocImmune mice that...
A CD3 bispecific antibody targeting Mucin 16 shows preclinical efficacy in mouse tumor models and a tolerable safety profile nonhuman primates.
EGFR blocking antibodies are approved for the treatment of colorectal cancer and head neck squamous cell carcinoma (HNSCC). Although ERBB3 signaling has been proposed to limit effectiveness inhibitors, underlying molecular mechanisms not fully understood. To gain insight into these mechanisms, we generated potent against (REGN1400) (REGN955). We show that coactivated in multiple HNSCC lines combined blockade inhibits growth more effectively than either receptor alone. Blockade with REGN955...
This report describes the cloning, expression and characterization of two members a novel human gene family proteins, HBNF MK, which exhibit neurite outgrowth-promoting activity. The cDNA codes for 168-residue protein is precursor previously described brain-derived heparin-binding 136 amino acids. second identified in this study, called 143-residue (including 22-amino acid signal sequence) 46% homologous with HBNF. Complementary DNA constructs coding mature MK proteins were expressed...
Abstract The Notch ligand delta-like 4 (Dll4) has been identified as a promising target in tumor angiogenesis preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. In this study, we report the development of REGN421 (enoticumab), fully human IgG1 monoclonal antibody that binds with sub-nanomolar affinity inhibits signaling. Administering to immunodeficient mice engineered express inhibited growth several xenografts...
We evaluated interleukin-6 (IL-6) receptor-α subunit (IL-6Rα) signaling inhibition with sarilumab and tocilizumab, the association between IL-6Rα receptor occupancy (RO) C-reactive protein (CRP), potential clinical relevance of any differences. For this, we measured binding tocilizumab in vitro, simulated soluble RO over time for approved subcutaneous (SC) intravenous (IV) SC doses, assessed associations calculated CRP reduction, 28-joint Disease Activity Score based on CRP, 20%/50%/70%...
ABSTRACT In our search for novel inhibitors of herpes simplex virus type 1 (HSV-1), a new class thiourea was discovered. N -{4-[3-(5-Chloro-2,4-dimethoxyphenyl)-thioureido]-phenyl}-acetamide and its 2-fluoro-benzamide derivative inhibited HSV-1 replication. HSV-2, human cytomegalovirus, varicella-zoster were to lesser extent. The compounds acted late in the replication cycle by impairing both cleavage concatameric viral DNA into progeny genome length packaging capsids, indicative defect...
Unrestrained IL-36R signaling in a humanized mouse model causes barrier impairment and increased cutaneous intestinal inflammation.
A series of nonnucleoside, N-alpha-methylbenzyl-N'-arylthiourea analogs were identified which demonstrated selective activity against varicella-zoster virus (VZV) but inactive other human herpesviruses, including herpes simplex virus. Representative compounds had potent VZV early-passage clinical isolates and an acyclovir-resistant isolate. Resistant viruses generated one inhibitor also resistant to in the series, suggesting that this group related small molecules was acting on same...
Recombinant HIV-1 Nef proteins with either thr-15 or ala-15 have been constructed and expressed in the T7 bacterial system. From soluble portion of lysates both Nef(thr-15) Nef(ala-15) purified to near homogeneity through 6 nondenaturing Chromatographic steps presence MgCl2. Neither display previously reported GTP binding activity. Additionally does not autophosphorylating activity [γ-32P]GTP [γ-32P]ATP. Although GTPase is present preparations proteins, it increase during purification...
The artemin-GFRα3 signaling pathway has been implicated in various painful conditions including migraine, cold allodynia, hyperalgesia, inflammatory bone pain, and mouse knees contain GFRα3-immunoreactive nerve endings. We developed high affinity (REGN1967) human (REGN5069) GFRα3-blocking monoclonal antibodies and, following vivo evaluations models of chronic joint pain (osteoarthritic-like inflammatory), conducted a first-in-human phase 1 pharmacokinetics (PK) safety trial REGN5069...
Abstract Angiopoietin-1 (Ang1) and -2 (Ang2) regulate angiogenesis via the endothelial cell-specific receptor tyrosine kinase Tie2. Blocking Ang2 binding to Tie2 decreases vessel density inhibits tumor growth in various human xenograft models. However, not all tumors respond blockade, which could be due high Ang1 levels acting as another ligand for Tie2, activities independent of or a weak role Ang-2/Tie2 signaling these tumors. To elucidate if plays an integral growth, we compared effects...
The retinoic acid-inducible MK gene shows a distinct developmental pattern of expression, which implies that it has potential growth regulation and differentiation functions, particularly in the brain. We report here cloning human from phage library constructed placental tissue. structure this been determined using Southern hybridization DNA sequence analysis. An isolated fragment was cloned found to contain sequences identical those previously cDNA clone, MKHC4. contains three introns...