A5103005014- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Trauma and Emergency Care Studies
- Genomics, phytochemicals, and oxidative stress
- Cancer-related Molecular Pathways
- Cardiac Arrest and Resuscitation
- Glutathione Transferases and Polymorphisms
- Medical Imaging and Analysis
- Immune Response and Inflammation
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Cell death mechanisms and regulation
- Venous Thromboembolism Diagnosis and Management
- Mitochondrial Function and Pathology
- Multiple Myeloma Research and Treatments
- Angiogenesis and VEGF in Cancer
- MicroRNA in disease regulation
- Genomics and Chromatin Dynamics
- Salmonella and Campylobacter epidemiology
- Viral-associated cancers and disorders
- Glycosylation and Glycoproteins Research
- Vitamin C and Antioxidants Research
Regeneron (United States)
2009-2023
Memorial Sloan Kettering Cancer Center
2020
Cornell University
2020
Case Western Reserve University
2019-2020
University Hospitals of Cleveland
2019-2020
University School
2019-2020
Stryker (United States)
2019
Cedars-Sinai Medical Center
2015-2018
California State University, San Marcos
2017
University of California, San Francisco
2015-2016
Interferons constitute the earliest immune response against viral infection. They elicit antiviral effects as well multiple biological responses involved in cell growth regulation and activation. Because interferon-induced cellular is primary defense mechanism infection, many viruses have evolved strategies to antagonize inhibitory of interferon. Here, we demonstrate a strategy that Kaposi's sarcoma-associated herpesvirus uses block virus-mediated induction type I We found immediate-early...
Induction of interferon-alpha (IFNalpha) gene expression in virus-infected cells requires phosphorylation-induced activation the transcription factors IRF3 and IRF7. However, kinase(s) that targets these proteins has not been identified. Using a combined pharmacological genetic approach, we found none kinases tested was responsible for IRF phosphorylation infected with Newcastle disease virus (NDV). Although broad-spectrum kinase inhibitor staurosporine potently blocked -7 phosphorylation,...
Previous studies have demonstrated cell cycle-dependent specificities in the interactions of E2F proteins with Rb family members. We now show that formation an E2F-p130 complex is unique to cells a quiescent, G0 state. The does not reform when reenter proliferative state and cycle through G1. presence quiescent coincides E2F-mediated repression transcription E2F1 gene, we sites promoter are important as enter quiescence but play no apparent role cycling cells. In addition, decay requires...
Bispecific antibodies, while showing great therapeutic potential, pose formidable challenges with respect to their assembly, stability, immunogenicity, and pharmacodynamics. Here we describe a novel class of bispecific antibodies native human immunoglobulin format. The design exploits differences in the affinities isotypes for Protein A, allowing efficient large-scale purification. Using this format, generated antibody, REGN1979, targeting B cell marker, CD20, CD3 component T receptor, which...
Background Current measurements of multiple myeloma disease burden are suboptimal. Daratumumab is a monoclonal antibody that targets CD38, an antigen expressed on nearly all cells. Purpose To demonstrate preclinical and first-in-human application composed the native daratumumab labeled with positron-emitting radionuclide zirconium 89 (89Zr) through chelator deferoxamine (DFO), or 89Zr-DFO-daratumumab, for immunologic PET imaging myeloma. Materials Methods 89Zr-DFO-daratumumab was synthesized...
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...
Previous work has demonstrated the critical role for transcription repression in quiescent cells through action of E2F-Rb or E2F-p130 complexes. Recent studies have shown that at least one mechanism this involves recruitment histone deacetylase. Nevertheless, these also suggest other events likely contribute to E2F/Rb-mediated repression. Using a yeast two-hybrid screen identify proteins specifically interact with Rb-related p130 protein, we demonstrate p130, as well Rb, interacts protein...
Abstract Lymphocytes derived from mice deficient in STAT1 showed reduced apoptosis and enhanced proliferation vitro. To understand the involvement of observed reduction apoptosis, we examined levels caspase bcl-2 family genes that are involved cell survival and/or apoptosis. The 1 11, two enzymes both cytokine protein processing induction were STAT1−/− cells compared with wild-type. However, comparable mice. also displayed an following TCR stimulation. This hyperproliferation could not be...
Interferon regulatory factor 7 (IRF7) is an interferon (IFN)-inducible transcription required for activation of a subset IFN-α genes that are expressed with delayed kinetics following viral infection. IRF7 synthesized as latent protein and posttranslationally modified by phosphorylation in infected cells. Phosphorylation carboxyl-terminal domain controlled the retention active exclusively nucleus, well its binding to specific DNA target sequences, multimerization, ability induce gene...
Type I interferon (IFN) is synthesized by most nucleated cells following viral infection. Robust IFN production in cell culture requires positive feedback expression of inducible signaling components, such as the transcription factor IRF7. However, role and IRF7 vivo may be more complex. We found that produced locally respiratory tract influenza virus-infected mice displayed characteristics feedback, including Stat1-dependent induction gene expression. was similarly stimulus-dependent...
Antibodies cross-linking the CD28 costimulatory pathway and a target antigen on tumors potentiate effects of checkpoint immunotherapy.
CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient to recognize kill tumors. Here we describe a fully human bsAb (REGN5458) that binds B-cell maturation (BCMA) CD3, compare its antitumor activities vs those of anti-BCMA CAR identify differences in efficacy mechanism action. In vitro, BCMAxCD3 efficiently induced polyclonal T-cell killing primary plasma multiple myeloma (MM) cell lines expressing...
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...
Abstract Patients with hematologic cancers have improved outcomes after treatment bispecific antibodies that bind to CD3 on T cells and redirect toward cancer cells. However, clinical benefit against solid tumors remains be shown. We made a antibody targets both the common prostate tumor–specific antigen PSMA (PMSAxCD3) provide evidence for tumor inhibition in several preclinical models. Mice expressing human extracellular regions of were generated examine antitumor efficacy presence an...
Human illness due to Camplyobacter jejuni infection is closely associated with consumption of poultry products. We previously demonstrated a 50 % shift in allele frequency (phase variation) contingency gene Cj1139 (wlaN) during passage C. NCTC11168 populations through Ross 308 broiler chickens. hypothesized that phase variation genes chicken could promote subsequent colonization and disease humans. To test this hypothesis, we passaged strains NCTC11168, 33292, 81-176, KanR4 CamR2 chickens...