A5084718667- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Bacteriophages and microbial interactions
- SARS-CoV-2 and COVID-19 Research
- Immunodeficiency and Autoimmune Disorders
- Glycosylation and Glycoproteins Research
- Protein purification and stability
- vaccines and immunoinformatics approaches
- Virus-based gene therapy research
- Diabetes and associated disorders
- Chronic Lymphocytic Leukemia Research
- Nanopore and Nanochannel Transport Studies
- Viral Infections and Immunology Research
- Respiratory viral infections research
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- Inflammatory mediators and NSAID effects
- Microbial Metabolic Engineering and Bioproduction
- Animal Virus Infections Studies
- Metabolism and Genetic Disorders
- Advanced biosensing and bioanalysis techniques
- Bacterial Genetics and Biotechnology
GigaGen (United States)
2017-2024
Grifols (United States)
2023
Cabot (United States)
2017
University of California, Berkeley
2015-2016
Bioengineering Center
2016
Nature uses protein compartmentalization to great effect for control over enzymatic pathways, and the strategy has promise synthetic biology. In particular, encapsulation in nanometer-sized containers create nanoreactors potential elicit interesting, unexplored effects resulting from deviations well-understood bulk processes. Self-assembled shells are especially desirable their uniform structures ease of perturbation through genetic mutation. Here, we use MS2 capsid, a well-defined porous 27...
Virus-like particles are used to encapsulate drugs, imaging agents, enzymes, and other biologically active molecules in order enhance their function. However, the size of most virus-like is inflexible, precluding design appropriately sized containers for different applications. Here, we describe a chromatographic selection particle assembly. Using this selection, identified single amino acid substitution coat protein bacteriophage MS2 that mediates uniform switch geometry from T = 3 1...
Affinity-matured, functional anti-pathogen antibodies are present at low frequencies in natural human repertoires. These often excellent candidates for therapeutic monoclonal antibodies. However, mining antibody repertoires is a challenge. In this study, we demonstrate new method that uses microfluidics, yeast display, and deep sequencing to identify 247 natively paired single-chain variable fragments (scFvs), which were initially as rare 1 100,000 the Influenza A vaccination increased...
Immunization of mice followed by hybridoma or B-cell screening is one the most common antibody discovery methods used to generate therapeutic monoclonal (mAb) candidates. There are a multitude different immunization protocols that can an immune response in animals. However, extensive analysis repertoires these alternative has not been performed. In this study, we immunized transgenically express human antibodies with either programmed cell death 1 protein cytotoxic T-lymphocyte associated 4...
Conventionally, mouse hybridomas or well-plate screening are used to identify therapeutic monoclonal antibody candidates. In this study, we present an alternative hybridoma-based discovery that combines microfluidics, yeast single-chain variable fragment (scFv) display, and deep sequencing rapidly interrogate screen repertoires. We our approach on six wild-type mice 269 molecules bind programmed cell death protein 1 (PD-1), which were at average of in 2,000 the pre-sort scFv libraries. Two...
Deep sequencing and single-chain variable fragment (scFv) yeast display methods are becoming more popular for discovery of therapeutic antibody candidates in mouse B cell repertoires. In this study, we compare a deep scFv method that retains native heavy light chain pairing with related randomly pairs chain. We performed the studies humanized mouse, using interleukin 21 receptor (IL-21R) as test immunogen. identified 44 high-affinity binder 100 random method. 30% natively paired binders were...
Abstract Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) possess mutations that prevent antibody therapeutics from maintaining antiviral binding and neutralizing efficacy. Monoclonal antibodies (mAbs) shown to neutralize Wuhan-Hu-1 SARS-CoV-2 (ancestral) strain have reduced potency against newer variants. Plasma-derived polyclonal hyperimmune drugs improved neutralization breadth compared with mAbs, but lower titers require higher dosages for treatment. We...
Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins vaccinated or convalescent donors have been used in treating infections where no treatment is available. This especially important multi-epitope neutralization required to prevent the development of immune-evading viral mutants that can emerge upon with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, first-in-class recombinant therapeutic against SARS-CoV-2...
To discover therapeutically relevant antibody candidates, many groups use mouse immunization followed by hybridoma generation or B cell screening. One modern approach is to screen cells generating natively paired single chain variable fragment (scFv) display libraries in yeast. Such methods typically rely on soluble antigens for scFv library However, cell-surface targets are difficult express a protein format, complicating discovery. In this study, we developed humanized mouse-derived yeast...
ABSTRACT Anti-CTLA-4 antibodies such as ipilimumab were among the first immune-oncology agents to show significantly improved outcomes for patients. However, existing anti-CTLA-4 therapies fail induce a response in majority of patients and can severe, immune-related adverse events. It has been assumed that checkpoint inhibition, i.e., blocking interaction between CTLA-4 its ligands, is primary mechanism action ipilimumab. In this study we present evidence inhibition not efficacy antibodies....
ABSTRACT Plasma-derived polyclonal antibodies are polyvalent drugs used for many important clinical indications that require modulation of multiple drug targets simultaneously, including emerging infectious disease and transplantation. However, plasma-derived suffer problems, low potency, impurities, constraints on supply, batch-to-batch variation. In this study, we demonstrated proofs-of-concept a technology uses microfluidics molecular genomics to capture diverse mammalian antibody...
<h3>Background</h3> It has been assumed that the primary mechanism of action first generation anti-CTLA-4 therapies is blocking interaction between CTLA-4 and its B7 ligands, leading to enhanced T cell costimulation activity. However, in preclinical studies mAbs can induce effective anti-tumor activity via an Fc receptor dependent action, suggesting depletion intratumoral Tregs may be a major mAbs. Additionally, there evidence suggest blockade contributes immune related adverse events...
Abstract Purpose Most individuals with antibody deficiency (hypogammaglobulinemia) need immunoglobulin replacement therapy (IgG-RT) from healthy plasma donors to stay clear of infections. However, a small subset hypogammaglobulinemic patients do not require this substitution therapy. We set out investigate clinical conundrum by asking whether the peripheral B cell receptor repertoires differ between antibody-deficient who and IgG-RT. Methods sequenced analyzed IgG IgM heavy chain blood...
<h3>Background</h3> Anti-CTLA-4 antibodies, such as ipilimumab, were among the first immuno-oncology agents to provide significantly improved outcomes for patients. However, existing anti-CTLA-4 therapies fail induce a response in majority of patients, and can severe immune-related adverse events. It has been assumed that checkpoint inhibition, i.e., blocking interaction between CTLA-4 its B7 ligands (CD80 CD86), is primary mechanism action ipilimumab. Here we present non-clinical evidence...
Abstract Anti-CTLA-4 antibodies such as ipilimumab were among the first immuno-oncology agents to show significantly improved outcomes for patients. However, existing anti-CTLA-4 therapies fail induce a response in majority of patients and can severe, immune-related adverse events. It has been assumed that checkpoint inhibition, i.e., blocking interaction between CTLA-4 its ligands, is primary mechanism action ipilimumab. Here we present evidence inhibition may not be efficacy antibodies....