A5082831559- Cancer Immunotherapy and Biomarkers
- SARS-CoV-2 and COVID-19 Research
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Glioma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Cancer, Hypoxia, and Metabolism
- Systemic Lupus Erythematosus Research
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Asthma and respiratory diseases
- Bladder and Urothelial Cancer Treatments
- Ferroptosis and cancer prognosis
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Animal Virus Infections Studies
- Peptidase Inhibition and Analysis
- Lung Cancer Research Studies
- Immune cells in cancer
- Systemic Sclerosis and Related Diseases
- Lung Cancer Treatments and Mutations
- vaccines and immunoinformatics approaches
AstraZeneca (United States)
2019-2025
AstraZeneca (United Kingdom)
2023
Center for Translational Molecular Medicine
2022
The Barbara Ann Karmanos Cancer Institute
2006-2007
Wayne State University
2006-2007
Pennsylvania State University
2002-2007
University of Michigan
2006
The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life been shown to prophylactic therapeutic effects in animal models. Pharmacokinetic data humans indicate has approximately 90 days.In ongoing phase 3 trial, we enrolled adults (≥18 years age) who had increased risk inadequate response vaccination disease 2019 (Covid-19), exposure...
Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chiT-bet+ subset, with a unique expression profile including chemokine receptors consistent migration to target tissues, expanded in SLE patients, present nephrotic kidney, enriched for autoreactive specificities and correlates defined clinical manifestations. IL-21 can potently induce cells promote differentiation these into...
Despite the success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there remains a need for more prevention and treatment options individuals remaining at risk disease 2019 (COVID-19). Monoclonal antibodies (mAbs) against viral spike protein have potential to both prevent treat COVID-19 reduce death. Here, we describe AZD7442, combination two mAbs, AZD8895 (tixagevimab) AZD1061 (cilgavimab), that simultaneously bind distinct, nonoverlapping epitopes on receptor...
Abstract Purpose: To identify a predictive biomarker for durvalumab, an anti–programmed death ligand 1 (PD-L1) mAb. Experimental Design: RNA sequencing of 97 advanced-stage non–small cell lung carcinoma (NSCLC) biopsies from nonrandomized phase Ib/II clinical trial (1108/NCT01693562) were profiled to signature; 62 locally advanced or metastatic urothelial cancer tumors the same study confirm utility signature. Thirty NSCLC patients provided pre- and posttreatment messenger (mRNA) analysis....
Small cell lung cancer (SCLC) is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly the Asian patient population. Here we conducted whole exome (WES) and transcriptomic primary tumors from 99 Chinese SCLC patients. Dysregulation tumor suppressor TP53 RB1 was observed 82% 62% patients, respectively, more than half patients (62%)...
Objectives To characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic clinical subgroups. Methods We performed post hoc analyses pooled data from 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials intravenous moderate-to-severe SLE. Outcomes were assessed predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age onset, glucocorticoid use,...
Treatment with anti–PD-1 and anti-PD-L1 therapies has shown durable clinical benefit in non–small cell lung cancer (NSCLC). However, patients NSCLC epidermal growth factor receptor (EGFR) mutations do not respond as well to treatment without an EGFR mutation. We show that EGFR-mutated expressed higher levels of CD73 compared WT tumors expression was regulated by signaling. lines were significantly more resistant T killing through suppression proliferation function. In a xenograft mouse model...
Objective The molecular basis of inflammatory myopathies such as dermatomyositis (DM), polymyositis, and inclusion body myositis, which share the characteristics chronic muscle inflammation skeletal wasting, are poorly understood. As such, effective targeted treatments for these diseases lacking, resulting in critical unmet medical needs devastating diseases. purpose this study was to identify possible new targets drug development by exploring mechanism may play a role pathology myopathies....
VIB4920, a nonantibody scaffold protein, blocks CD40L and reduces autoantibodies disease activity in patients with rheumatoid arthritis.
Abstract The 8p11-p12 genomic region is amplified in 15% of breast cancers and harbors several candidate oncogenes. However, functional evidence for a transforming role these genes lacking. We identified 21 from this as potential oncogenes based on statistical association between copy number expression. further showed that three (LSM1, BAG4, C8orf4) induce transformed phenotypes when overexpressed MCF-10A cells, overexpression combination influences the growth factor independence phenotype...
Systemic sclerosis (SSc) is a clinically heterogeneous, life-threatening disease characterized by fibrosis, microvasculopathy, and autoimmunity. Extensive nonclinical clinical data implicate B cells in the pathogenesis of SSc. MEDI-551 an investigational humanized monoclonal antibody that targets cell surface antigen CD19 mediates antibody-dependent, cell-mediated cytotoxicity cells. This study evaluated safety tolerability, pharmacokinetics, pharmacodynamics subjects with phase I...
Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occur. New immunomodulatory targets, which are highly expressed in activated immune cells, needed. MEDI0562, an agonistic humanized mAb, specifically binds to the costimulatory molecule OX40. This first-in-human study evaluated MEDI0562 adults with advanced tumors.In this phase I, multicenter, open-label, single-arm, dose-escalation (3+3 design) study,...
Expression profiling of microRNAs in melanoma lesional skin biopsies compared with normal donor biopsies, as well cell lines melanocytes, revealed that hsa-miR-206 was down-regulated (-75.4-fold, P = 1.7 × 10(-4)). MiR-206 has been implicated a large number cancers, including breast, lung, colorectal, ovarian, and prostate cancers; however, its role tumor development remains largely unknown, biologic function is poorly characterized, targets affecting cancer cells are unknown. reduced growth...
Production of pathogenic autoantibodies by self-reactive plasma cells (PCs) is a hallmark autoimmune diseases. We undertook this study to investigate the prevalence PCs and their relationship known pathways increase our understanding role in disease progression treatment response.We developed sensitive gene expression-based method overcome challenges measuring using flow cytometry. Whole-genome microarray analysis sorted cellular fractions identified panel genes, IGHA1, IGJ, IGKC, IGKV4-1,...
This phase 3 trial assessed AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis against symptomatic coronavirus disease 2019 (COVID-19).Adults without prior severe acute respiratory syndrome 2 (SARS-CoV-2) infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2-infected individual and randomized 2:1 single 300-mg dose (one 1.5-mL intramuscular injection each tixagevimab cilgavimab) placebo. Primary end points safety first post-dose SARS-CoV-2...
Abstract Purpose: Combination therapies targeting immunologic checkpoints have shown promise in treating multiple tumor types. We report safety and tolerability of MEDI0562, a humanized IgG1K OX40 mAb, combination with durvalumab (anti-PD-L1), or tremelimumab (anti-CTLA-4), adult patients previously treated advanced solid tumors. Patients Methods: In this phase I, multicenter, open-label study, received escalating doses MEDI0562 (2.25, 7.5, 22.5 mg) every 2 weeks (1,500 (75 225 4 weeks,...
Therapeutic anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (MAbs) provide immunosuppressed and vulnerable populations with prophylactic treatment interventions against disease 2019 (COVID-19). AZD7442 (tixagevimab-cilgavimab) is a combination of extended-half-life neutralizing MAbs that bind to distinct epitopes on the receptor binding domain (RBD) SARS-CoV-2 spike protein. The Omicron variant concern carries mutations at >35 positions in protein has...
Abstract Background AZD7442 is a combination of extended half-life, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)−specific neutralizing monoclonal antibodies (tixagevimab and cilgavimab). Methods This phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study evaluated administered intramuscularly (300 mg) or intravenously (300, 1000, 3000 in healthy adults (aged 18–55 years). The primary end point was safety tolerability. Secondary points...
Abstract We have recently shown that an amphiregulin-mediated autocrine loop is responsible for growth factor–independent proliferation, motility, and invasive capacity of some aggressive breast cancer cells, such as the SUM149 cell line. In present study, we investigated mechanisms by which amphiregulin activation epidermal factor receptor (EGFR) regulates these altered phenotypes. Bioinformatic analysis gene expression networks regulated implicated interleukin-1α (IL-1α) IL-1β key...