A5087819473- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Glycosylation and Glycoproteins Research
- Genetics and Neurodevelopmental Disorders
- Nuclear Receptors and Signaling
- Protein purification and stability
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Radiopharmaceutical Chemistry and Applications
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Click Chemistry and Applications
- Galectins and Cancer Biology
- Synthesis and pharmacology of benzodiazepine derivatives
- PARP inhibition in cancer therapy
- Bacteriophages and microbial interactions
- Cancer therapeutics and mechanisms
- Chronic Lymphocytic Leukemia Research
- Advanced biosensing and bioanalysis techniques
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- Axon Guidance and Neuronal Signaling
- RNA Interference and Gene Delivery
Columbia University
2025
AstraZeneca (United States)
2019-2023
Protein Express (United States)
2018
Scripps Research Institute
1996-2004
Torrey Pines Institute For Molecular Studies
2004
University of California, Los Angeles
1998
Shanghai CASB Biotechnology (China)
1996
A new antibody platform combining anti-Psl and anti-PcrV activities provides enhanced protection acts synergistically with antibiotics against Pseudomonas aeruginosa .
The first three-dimensional structure of a human Fc fragment genetically engineered for the elimination its ability to mediate antibody-dependent cell-mediated cytotoxicity and complement-dependent is reported. When introduced into lower hinge CH2 domain IgG1 molecules, triple mutation L234F/L235E/P331S ('TM') causes profound decrease in their binding CD64, CD32A, CD16 C1q. Enzymatically produced Fc/TM was crystallized solved at resolution 2.3 A using molecular replacement. This study...
Abstract The EphA2 receptor tyrosine kinase is selectively expressed on the surface of many different human tumors. We have previously shown that tumor cells can be targeted by monoclonal antibodies and these function, in part, inducing internalization degradation. In this report, we describe isolation characterization a fully antibody (1C1) binds both rodent receptor. After cell binding, induces rapid phosphorylation, internalization, degradation Because bind internalize provide vehicle for...
T follicular helper–like cells and IL-21 are drivers of skin fibrosis in systemic sclerosis.
The gene VII protein (pVII) and IX (pIX) are associated closely on the surface of filamentous bacteriophage that is opposite end harboring widely exploited pIII protein. We developed a phagemid format wherein antibody heavy- light-chain variable regions were fused to amino termini pVII pIX, respectively. Significantly, fusion proteins interacted form functional Fv-binding domain phage surface. Our approach will be applicable display generic peptide libraries can combinatorial heterodimeric...
A highly specific Diels-Alder protein catalyst was made by manipulating the antibody repertoire of immune system. The catalytic 13G5 catalyzes a disfavored exo transformation in reaction for which there is no natural enzyme counterpart and that yields single regioisomer high enantiomeric excess. crystal structure Fab complex with ferrocenyl inhibitor containing essential haptenic core elicited determined at 1.95 angstrom resolution. Three key residues appear to be responsible observed...
Antibody–drug conjugates (ADCs) are a class of biopharmaceuticals that combine the specificity antibodies with high-potency cytotoxic drugs. Engineering cysteine residues in using mutagenesis is common method to prepare site-specific ADCs. With this approach, solvent accessible amino acids antibody have been selected for substitution conjugating maleimide-bearing drugs, resulting homogeneous and stable Here we describe engineering approach based on insertion cysteines before after sites...
The thiol–maleimide linkage is widely used for antibody–drug conjugate (ADC) production; however, conjugation of maleimide–drugs could be improved by simplified procedures and reliable stability. Here, we report the evaluation electron-rich cyclic dienes that can appended to antibodies reacted with maleimide-containing drugs through Diels–Alder (DA) reaction. Drug fast quantitative due reaction acceleration in water, more stable serum than corresponding adduct same drug. ADCs produced using...
For more than a decade, phage displayed combinatorial antibody libraries have been used to generate and select wide variety of antibodies. We previously reported that the coat proteins pVII pIX could be display heterodimeric structure Fv region. Herein, aspects this technology were invoked extended construct large, human single-chain (scFv) library 4.5 × 10 9 members on filamentous bacteriophage. Furthermore, diversity, quality, utility demonstrated by selection scFv clones against six...
The humanized monoclonal antibody Abegrin, currently in phase II trials for treatment of solid tumors, specifically recognizes the integrin alphavbeta3. Due to its high expression on mature osteoclasts, angiogenic endothelial cells, and tumor alphavbeta3 functions several pathologic processes important growth metastasis. Targeting this with Abegrin results antitumor, antiangiogenic, antiosteolytic activities. Here, we exploit species specificity evaluate effects direct targeting cells...
A drawback of targeting soluble antigens such as cytokines or toxins with long-lived antibodies is that can prolong the half-life target antigen by a "buffering" effect. This has motivated design bind to higher affinity at near neutral pH relative acidic endosomal (~pH 6.0). Such are expected release within endosomes following uptake into cells, whereas antibody will be recycled and exocytosed in FcRn-expressing cells. To understand how dependence antibody-antigen interactions affects...
ADAM17 is the primary sheddase for HER pathway ligands. We report discovery of a potent and specific inhibitory antibody, MEDI3622, which induces tumor regression or stasis in many EGFR-dependent models. The activity MEDI3622 correlated with EGFR both series models across several indications as well focused set head neck patient-derived xenograft antitumor was superior to that EGFR/HER inhibitors OE21 esophageal model COLO205 colorectal suggesting additional outside pathway. Combination...
mAbs against tumor-associated carbohydrate antigens have the potential to play a prominent role in cancer immunotherapy. However, it has not been possible fully exploit clinical utility of such antibodies primarily, because those adequate affinity could be derived only from murine sources. To address this problem, we prepared single-chain Fv (scFv) antibody library peripheral blood lymphocytes 20 patients with various diseases. Completely human high-affinity scFv were then selected by using...
Abstract B cell activation is regulated by a variety of signals. CD19 positively regulates activation, augmenting signals delivered through the BCR complex. In contrast, CD32b contains an ITIM and negatively signaling. Importantly, there are drugs currently in clinical trials preclinical development that cross-link to molecules within We wanted address how single engagement versus cotargeting these affects human function. When cells from healthy individuals were activated mimic T response...
Targeted nanomedicines are a promising technology for treatment of disease; however, preparation and characterization well-defined protein-nanoparticle systems remain challenging. Here, we describe platform to prepare antibody binding fragment (Fab)-bearing nanoparticles an accompanying real-time cell-based assay determine their cellular uptake compared monoclonal antibodies (mAbs) Fabs. The nanoparticle was composed core-cross-linked polyion complex (PIC) micelles prepared from...
Antibody–drug conjugates (ADCs) have become a powerful platform to deliver cytotoxic agents selectively cancer cells. ADCs traditionally been prepared by stochastic conjugation of drug using an antibody's native cysteine or lysine residues. Through strategic selection the mammalian expression host, we were able introduce azide-functionalized glycans onto homogeneously glycosylated anti-EphA2 monoclonal antibody in one step. Conjugation with alkyne-bearing pyrrolobenzodiazepine dimer payload...