A5032863821- Monoclonal and Polyclonal Antibodies Research
- Toxin Mechanisms and Immunotoxins
- Bacteriophages and microbial interactions
- Microbial infections and disease research
- Protein purification and stability
- Transgenic Plants and Applications
- HIV Research and Treatment
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Microbial Inactivation Methods
- Viral Infectious Diseases and Gene Expression in Insects
- Galectins and Cancer Biology
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- COVID-19 Clinical Research Studies
- Mycotoxins in Agriculture and Food
- SARS-CoV-2 detection and testing
- Immunotherapy and Immune Responses
AstraZeneca (United States)
2022-2025
Center for Cancer Research
2015-2018
Tel Aviv University
2011-2017
National Institutes of Health
2015-2017
National Cancer Institute
2015-2016
Over the past two decades, therapeutic antibodies have emerged as a rapidly expanding domain within field of biologics. In silico tools that can streamline process antibody discovery and optimization are critical to support pipeline is growing more numerous complex every year. High-quality structural information remains for process, but antibody-antigen structures often unavailable in docking methods still unreliable. this study, DeepAb, deep learning model predicting Fv structure directly...
Experimental screening for biopharmaceutical developability properties typically relies on resource-intensive, and time-consuming assays such as size exclusion chromatography (SEC). This study highlights the potential of in silico models to accelerate process by exploring sequence structure-based machine learning techniques. Specifically, we compared surrogate based pre-computed features extracted from predicted structure with sequence-based approaches using protein language (PLMs) like...
Most previously authorized clinical antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have lost neutralizing activity to recent variants due rapid viral evolution. To mitigate such escape, we preemptively enhance AZD3152, an antibody for prophylaxis in immunocompromised individuals. Using deep mutational scanning (DMS) on the SARS-CoV-2 antigen, identify AZD3152 vulnerabilities at antigen positions F456 and D420. Through two iterations of computational design...
Highly concentrated antibody solutions are necessary for developing subcutaneous injections but often exhibit high viscosities, posing challenges in antibody-drug development, manufacturing, and administration. Previous computational models were only limited to a few dozen data points training, bottleneck generalizability. In this study, we measured the viscosity of panel 229 monoclonal antibodies (mAbs) develop predictive concentration mAb screening. We developed DeepViscosity, consisting...
Background Polyclonal serum consists of vast collections antibodies, products differentiated B-cells. The spectrum antibody specificities is dynamic and varies with age, physiology, exposure to pathological insults. complete repertoire in blood, the IgOme, therefore an extraordinarily rich source information–a molecular record previous encounters as well a status report current immune activity. ability profile polyclonal at exceptionally high resolution has been important serious challenge...
Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several that have evaluated in clinical trials. Immunogenicity the bacterial toxin off-target toxicity limited efficacy these immunotoxins. To address issues, we previously made RITs which Fv is connected domain III (PE24) by furin cleavage site (FCS), thereby removing unneeded sequences II. However, PE24 containing do not contain naturally occurring...
The HIV envelope binds cellular CD4 and undergoes a range of conformational changes that lead to membrane fusion delivery the viral nucleocapsid into cytoplasm. This binding reveals cryptic highly conserved epitopes, molecular nature which is still not fully understood. atomic structures complexed with gp120 core molecules (a form in V1, V2, V3 loops N C termini have been truncated) indicated hallmark feature CD4-bound conformation bridging sheet minidomain. Variations orientation hairpins...
Abstract Tac (CD25) is expressed on multiple hematologic malignancies and a target for cancer therapies. LMB-2 an extremely active anti-Tac recombinant immunotoxin composed of Fv that binds to 38-kDa fragment Pseudomonas exotoxin A (PE38). Although has shown high cytotoxicity toward Tac-expressing cells in clinical trials, its efficacy was hampered by the formation anti-drug antibodies against immunogenic bacterial toxin dose-limiting off-target toxicity. To reduce immunogenicity nonspecific...
The CD4-induced (CD4i) epitopes in gp120 includes the co-receptor binding site, which are formed and exposed after interaction with CD4. Monoclonal antibodies (mAbs) to CD4i exhibit limited neutralizing activity because of restricted access their epitopes. However, small fragment counterparts such as single-chain variable fragments (scFvs) have been reported neutralize a broad range viruses compared full-size IgG molecule. To identify epitope site responsible for this neutralization we...
Abstract Over the last two decades, therapeutic antibodies have emerged as a rapidly expanding domain within field biologics. In silico tools that can streamline process of antibody discovery and optimization are critical to support pipeline is growing more numerous complex every year. this study, DeepAb, deep learning model for predicting Fv structure directly from sequence, was used design 200 potentially stabilized variants an anti-hen egg lysozyme (HEL) antibody. We sought determine...
To combat the COVID-19 pandemic, potential therapies have been developed and moved into clinical trials at an unprecedented pace. Some of most promising are neutralizing antibodies against SARS-CoV-2. In order to maximize therapeutic effectiveness such antibodies, Fc engineering modulate effector functions extend half-life is desirable. However, it critical that does not negatively impact developability properties as these play a key role in ensuring rapid development, successful...
Abstract Background HIV-1 infection of target cells is mediated via the binding viral envelope protein, gp120, to cell surface receptor CD4. This interaction leads conformational rearrangements in gp120 forming or revealing CD4 induced (CD4i) epitopes which are critical for subsequent recognition co-receptor required entry. The CD4-bound state has been considered a potential immunogen vaccine development. Here we report on an alternative means induce into CD4i conformation. Results...
AZD7442, a combination of two long-acting monoclonal antibodies (tixagevimab [AZD8895] and cilgavimab [AZD1061]), has been authorized for the prevention treatment coronavirus disease 2019 (COVID-19). The rapid emergence severe acute respiratory syndrome 2 (SARS-CoV-2) variants requires methods capable quickly characterizing resistance to AZD7442. To support AZD7442 monitoring, biolayer interferometry (BLI) assay was developed screen binding tixagevimab SARS-CoV-2 spike proteins reduce number...
The HIV envelope binds cellular CD4 and undergoes a series of conformational changes that lead to membrane fusion delivery the viral nucleocapsid into cytoplasm. This binding CD4, reveals cryptic highly conserved epitopes, molecular nature which are still not fully understood. atomic structures complexed with gp120 core molecules (truncations V1, V2, V3 N C termini) have indicated hallmark feature CD4-bound conformation is “bridging sheet” mini-domain. Here we describe analyses state using...
Abstract Objective: CD25 is expressed on many T cell malignancies, including adult leukemia, and a target for cancer therapy. Immunotoxins against CD25+ cells containing portion of Pseudomonas exotoxin A (PE38) show extremely high cytotoxic activity. Our lab has previously created de-immunized PE immunotoxin in which toxin domain II was removed. Removal confers two major advantages: i) the immunogenic sequences found are removed, generating less toxin; ii) non-specific toxicity II-truncated...
<div>Abstract<p>Tac (CD25) is expressed on multiple hematologic malignancies and a target for cancer therapies. LMB-2 an extremely active anti-Tac recombinant immunotoxin composed of Fv that binds to Tac 38-kDa fragment <i>Pseudomonas</i> exotoxin A (PE38). Although has shown high cytotoxicity toward Tac-expressing cells in clinical trials, its efficacy was hampered by the formation anti-drug antibodies against immunogenic bacterial toxin dose-limiting off-target...
<p>Production and screening of ZZ-PE mutant fusion proteins</p>
<p>Illustrations of the rationally designed domain II truncation mutants</p>
<p>Production and screening of ZZ-PE mutant fusion proteins</p>
<p>Illustrations of the rationally designed domain II truncation mutants</p>
<div>Abstract<p>Tac (CD25) is expressed on multiple hematologic malignancies and a target for cancer therapies. LMB-2 an extremely active anti-Tac recombinant immunotoxin composed of Fv that binds to Tac 38-kDa fragment <i>Pseudomonas</i> exotoxin A (PE38). Although has shown high cytotoxicity toward Tac-expressing cells in clinical trials, its efficacy was hampered by the formation anti-drug antibodies against immunogenic bacterial toxin dose-limiting off-target...
Sessions C543process is known as a method of synthesizing homogeneous Nd 2 Fe 14 B single phase powders [2].In the HDDR process, grains disproportionate into mixture α-Fe, NdH and by hydrogenation under high temperature hydrogen atmosphere.The subsequent desorption results in recombination sub-micron grains.On other hand, nano-structurization Nd-Fe-B alloys reactive mechanical milling have been successfully performed [3,4], therefore, synthesis nano-structure expected to be fulfilled [5].In...