A5008369148- Monoclonal and Polyclonal Antibodies Research
- Fibroblast Growth Factor Research
- Eosinophilic Disorders and Syndromes
- Kruppel-like factors research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Complement system in diseases
- Angiogenesis and VEGF in Cancer
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Asthma and respiratory diseases
- Protein purification and stability
- Nanoparticle-Based Drug Delivery
- Bladder and Urothelial Cancer Treatments
- Dermatology and Skin Diseases
- Lipid metabolism and disorders
- Colorectal Cancer Treatments and Studies
- Blood groups and transfusion
- Cancer, Hypoxia, and Metabolism
- Renal Diseases and Glomerulopathies
- Viral Infections and Outbreaks Research
Regeneron (United States)
2015-2025
City of Hope
2004
Beckman Research Institute
2004
Florida College
2004
University of Florida
2004
City Of Hope National Medical Center
2004
BioScience Laboratories (United States)
1999
National Cancer Institute
1999
Vascular endothelial growth factor (VEGF) plays a critical role during normal embryonic angiogenesis and also in the pathological that occurs number of diseases, including cancer. Initial attempts to block VEGF by using humanized monoclonal antibody are beginning show promise human cancer patients, underscoring importance optimizing blockade. Previous studies have found one most effective ways VEGF-signaling pathway is prevent from binding its receptors administering decoy-soluble receptors....
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,...
The angiopoietins have recently joined the members of vascular endothelial growth factor family as only known factors largely specific for endothelium. include a naturally occurring agonist, angiopoietin-1, well antagonist, angiopoietin-2, both which act by means Tie2 receptor. We now report our attempts to use homology-based cloning approaches identify new angiopoietin family. These efforts led identification two angiopoietins, angiopoietin-3 in mouse and angiopoietin-4 human; we also...
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...
Abstract Background Dupilumab, a fully human monoclonal antibody that binds IL‐4Rα and inhibits signaling of both IL‐4 IL‐13, has shown efficacy across multiple diseases with underlying type 2 signatures is approved for treatment asthma, atopic dermatitis, chronic sinusitis nasal polyposis. We sought to provide comprehensive analysis the redundant distinct roles IL‐13 in inflammation report dupilumab mechanisms action. Methods Using primary cell assays mouse model house dust mite–induced we...
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....
Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased IgG, thought competitively block allergen binding IgE. Here we show that blocking potency IgG response Cat-SIT heterogeneous. Next, using two potent, pre-selected...
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...
The Programmed Death-1 (PD-1) receptor delivers inhibitory checkpoint signals to activated T cells upon binding its ligands PD-L1 and PD-L2 expressed on antigen-presenting cancer cells, resulting in suppression of T-cell effector function tumor immune evasion. Clinical antibodies blocking the interaction between PD-1 restore cytotoxic antigen-specific yielding durable objective responses multiple cancers. This report describes preclinical characterization REGN2810, a fully human...
A CD3 bispecific antibody targeting Mucin 16 shows preclinical efficacy in mouse tumor models and a tolerable safety profile nonhuman primates.
CD28 bispecific antibodies are well tolerated and enhance the antitumor efficacy of CD3 bispecifics as a potential off-the-shelf antibody therapy.
BackgroundSevere inflammatory airway diseases are associated with inflammation that does not resolve, leading to structural changes and an overall environment primed for exacerbations.ObjectiveWe sought identify inhibit pathways perpetuate this heightened state because could lead therapies allow a more quiescent lung is less predisposed symptoms exacerbations.MethodsUsing prolonged exposure house dust mite in mice, we developed mouse model of persistent exacerbating disease characterized by...
Abstract T-cell-redirecting bispecific antibodies have emerged as a new class of therapeutic agents designed to simultaneously bind T cells via CD3 and tumor tumor-cell-specific antigens (TSA), inducing T-cell-mediated killing cells. The promising preclinical clinical efficacy TSAxCD3 is often accompanied by toxicities such cytokine release syndrome due T-cell activation. How the toxicity profile depends on binding affinity remains unclear. Here, we evaluate that were engineered range...
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...
Complement is a key component of the innate immune system. Inappropriate complement activation underlies pathophysiology variety diseases. 5 (C5) validated therapeutic target for complement-mediated diseases, but development new therapeutics has been limited by paucity preclinical models to evaluate pharmacokinetic (PK) and pharmacodynamic (PD) properties candidate therapies. The present report describes novel humanized C5 mouse its utility in evaluating panel fully human anti-C5 antibodies....
The common γ chain (γc; IL-2RG) is a subunit of the interleukin (IL) receptors for γc cytokines IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. lack appropriate neutralizing antibodies recognizing IL-2RG has made it difficult to thoroughly interrogate role in inflammatory autoimmune disease settings. Here, we generated cytokine receptor antibody, REGN7257, determine whether might be targeted T cell–mediated prevention treatment. Biochemical, structural, vitro analysis showed that REGN7257 binds...
Anti-vascular endothelial growth factor (VEGF) therapies have improved clinical outcomes for patients with cancers and retinal vascular diseases. Three anti-VEGF agents, pegaptanib, ranibizumab, aflibercept, are approved ophthalmic indications, while bevacizumab is to treat colorectal, lung, renal cancers, but also used off-label ocular The efficacy of relative ranibizumab in treating neovascular age-related macular degeneration has been assessed several trials. However, questions persist...
Surface plasmon resonance (SPR) is a well-established method to characterize biomolecular interactions and widely used in drug discovery development. Here, we demonstrate that capture surfaces profoundly impact the binding kinetics parameters are measured for antibody-antigen interactions. Six unique were characterized using eight different anti-human IgG surfaces. The antigen affinities six human monoclonal antibodies (hmAbs) captured three goat Fc (AHC) polyclonal antibody (pAb) reasonable...
Unrestrained IL-36R signaling in a humanized mouse model causes barrier impairment and increased cutaneous intestinal inflammation.
Deficiency in the adipose-derived hormone leptin or receptor signaling causes class 3 obesity individuals with genetic loss-of-function mutations its LEPR and metabolic liver disease hypoleptinemia secondary to lipoatrophy such as generalized lipodystrophy. Therapies that restore leptin-LEPR may resolve these sequelae. We developed a fully human monoclonal antibody (mAb), REGN4461 (mibavademab), activates absence presence of leptin. In obese knockout mice, normalized body weight, food...
<h3>Background</h3> Sarilumab is the first fully human monoclonal antibody (mAb) directed against interleukin-6 receptor alpha (IL-6Rα). was developed using VelocImmune<sup>®</sup> mice immunized with IL-6 (hIL-6) receptor. VelocImmune are genetically-engineered to express variable domain genes in same robust fashion that replaced mouse typically expressed. currently being explored as a new therapeutic modality for treatment of rheumatoid arthritis. <h3>Objectives</h3> To evaluate kinetic...