A5017367178- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- HER2/EGFR in Cancer Research
- Prostate Cancer Treatment and Research
- Immune Cell Function and Interaction
- Eosinophilic Disorders and Syndromes
- Fibroblast Growth Factor Research
- Radiopharmaceutical Chemistry and Applications
- HIV/AIDS drug development and treatment
- CAR-T cell therapy research
- Kruppel-like factors research
- Peptidase Inhibition and Analysis
- Advanced Biosensing Techniques and Applications
- Glycosylation and Glycoproteins Research
- Nanofabrication and Lithography Techniques
- Hepatitis C virus research
- Neuroblastoma Research and Treatments
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Liver physiology and pathology
- Herpesvirus Infections and Treatments
- Mass Spectrometry Techniques and Applications
Regeneron (United States)
2016-2025
Progenics Pharmaceuticals (United States)
2007-2019
Icahn School of Medicine at Mount Sinai
2017
Institut thématique Génétique, génomique et bioinformatique
2017
Janssen (United States)
2017
Janssen Scientific Affairs (United States)
2014-2017
Mental Health Association of Westchester County
2014
Janssen (Belgium)
2014
Dana-Farber Cancer Institute
2011-2012
Cleveland Clinic
2003-2012
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 HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with coat. Crystal structures antigen-binding fragments (Fabs) 127 and 128 Man(9) at 1.65 1.29 angstrom resolution, respectively, binding data delineate specific high mannose-binding site. Fab complexed fully glycosylated outer domain 3.25 angstroms reveals that penetrates shield...
Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets.
The few antibodies that can potently neutralize human immunodeficiency virus type 1 (HIV-1) recognize the limited number of envelope glycoprotein epitopes exposed on infectious virions. These native complexes comprise three gp120 subunits noncovalently and weakly associated with gp41 moieties. individual induce neutralizing inefficiently but raise many nonneutralizing antibodies. Consequently, recombinant glycoproteins do not elicit strong antiviral antibody responses, particularly against...
ABSTRACT The envelope glycoprotein (Env) complex of human immunodeficiency virus type 1 has evolved a structure that is minimally immunogenic while retaining its natural function receptor-mediated virus-cell fusion. Env trimeric; six individual subunits (three gp120 and three gp41 subunits) are associated by relatively weak, noncovalent interactions. induction neutralizing antibodies after vaccination with proven very difficult, probably because they inadequate mimics the native complex. Our...
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...
ABSTRACT It is well established that the gp120 V3 loop of T-cell-line-adapted human immunodeficiency virus type 1 (HIV-1) binds both cell-associated and soluble polyanions. Virus infectivity increased by interactions between HIV-1 heparan sulfate proteoglycans on some cell types, polyanions such as heparin dextran neutralize in vitro. However, analysis gp120-polyanion has been limited to T-cell-line-adapted, CXCR4-using virus-derived gp120, polyanion binding ability regions other than not...
Hepatitis C virus (HCV) infects nearly 3% of the population world and is a major cause liver disease. However, mechanism whereby targets for infection remains unknown, because none putative cellular receptors HCV are both expressed specifically in capable binding envelope glycoproteins. Liver/lymph node-specific intercellular adhesion molecule-3-grabbing integrin (L-SIGN) calcium-dependent lectin on endothelial cells lymph nodes. Dendritic cell-specific nonintegrin (DC-SIGN), homologous...
Prostate-specific membrane antigen (PSMA) is a type 2 integral glycoprotein that serves as an attractive target for cancer immunotherapy by virtue of its abundant and restricted expression on the surface prostate carcinomas neovasculature most other solid tumors. However, relatively little known about molecular structure this target. Here, we report PSMA expressed tumor cells noncovalent homodimer. A truncated protein, lacking transmembrane cytoplasmic domains, also formed homodimers,...
ABSTRACT CCR5 serves as a requisite fusion coreceptor for clinically relevant strains of human immunodeficiency virus type 1 (HIV-1) and provides promising target antiviral therapy. However, no study to date has examined whether monoclonal antibodies, small molecules, or other nonchemokine agents possess broad-spectrum activity against the major genetic subtypes HIV-1. PRO 140 (PA14) is an anti-CCR5 antibody that potently inhibits HIV-1 entry at concentrations do not affect CCR5's chemokine...
ABSTRACT The CC-chemokine receptor CCR5 mediates fusion and entry of the most commonly transmitted human immunodeficiency virus type 1 (HIV-1) strains. We have isolated six new anti-CCR5 murine monoclonal antibodies (MAbs), designated PA8, PA9, PA10, PA11, PA12, PA14. A panel alanine point mutants was used to map epitopes these MAbs previously described MAb 2D7 specific amino acid residues in N terminus and/or second extracellular loop regions CCR5. This structural information correlated...
ABSTRACT The CC-chemokine receptor CCR5 is required for the efficient fusion of macrophage (M)-tropic human immunodeficiency virus type 1 (HIV-1) strains with plasma membrane CD4 + cells and interacts directly viral surface glycoprotein gp120. Although chimera studies have provided useful information, domains that function HIV-1 entry, including site gp120 interaction, not been unambiguously identified. Here, we use site-directed, alanine-scanning mutagenesis to show substitutions negatively...
Target cell tropism of enveloped viruses is regulated by interactions between viral and cellular factors during transmission, dissemination, replication within the host. Binding envelope glycoproteins to specific cell-surface receptors determines susceptibility entry. However, a number molecules bind without mediating Instead, they serve as capture that disseminate particles target organs or susceptible cells. We others recently demonstrated C type lectins L-SIGN DC-SIGN hepatitis virus...
Human immunodeficiency virus type 1 (HIV-1) subtype C viruses with different coreceptor usage profiles were isolated from 29 South African patients advanced AIDS. All 24 R5 isolates inhibited by the CCR5-specific agents, PRO 140 and RANTES, while two X4 three R5X4 sensitive to CXCR4-specific inhibitor, AMD3100. The five or all able replicate in peripheral blood mononuclear cells that did not express CCR5. When tested using coreceptor-transfected cell lines, one was also use CXCR6, another...
The initial step in HIV-1 infection occurs with the binding of cell surface CD4 to trimeric envelope glycoproteins (Env), a heterodimer transmembrane glycoprotein (gp41) and (gp120). design soluble versions Env that display structural functional properties similar those observed on intact viruses is highly desirable from viewpoint designing immunogens could be effective as vaccines against HIV/AIDS. Using cryoelectron tomography combined subvolume averaging, we have analyzed structure SOSIP...
The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is a vaccine immunogen that can signal via several cell surface receptors. To investigate whether receptor biology could influence immune responses to gp120, we studied its interaction with human, monocyte-derived dendritic cells (MDDCs) in vitro. Gp120 from the HIV-1 strain JR-FL induced IL-10 expression MDDCs 62% of donors, mannose C-type lectin receptor(s) (MCLR). LAI was also an inducer, but KNH1144 not....
The properties of cell surface proteins targeted by antibody-drug conjugates (ADCs) have not been fully exploited; particular importance are the rate internalization and route intracellular trafficking. In this study, we compared trafficking HER2, which is target clinically approved ADC ado-trastuzumab emtansine (T-DM1), with that prolactin receptor (PRLR), another potential in breast cancer. contrast to found PRLR rapidly constitutively internalized, traffics efficiently lysosomes, where it...
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.
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...