A5085633655- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- Prostate Cancer Treatment and Research
- PI3K/AKT/mTOR signaling in cancer
- Cytokine Signaling Pathways and Interactions
- Chronic Lymphocytic Leukemia Research
- Biosimilars and Bioanalytical Methods
- Advanced Biosensing Techniques and Applications
- Receptor Mechanisms and Signaling
- Cell Adhesion Molecules Research
- Nanofabrication and Lithography Techniques
- Peptidase Inhibition and Analysis
- Medical Imaging and Pathology Studies
- Ovarian cancer diagnosis and treatment
- Cancer Research and Treatments
- Cancer Treatment and Pharmacology
- Lung Cancer Treatments and Mutations
- Protein purification and stability
- Neuroscience and Neuropharmacology Research
- Ubiquitin and proteasome pathways
- Biosensors and Analytical Detection
- Phagocytosis and Immune Regulation
- Protein Kinase Regulation and GTPase Signaling
NGM Biopharmaceuticals (United States)
2018
Institute for In Vitro Sciences
2018
Genentech
2012-2014
Kaiser Permanente South San Francisco Medical Center
2012
Target (United States)
2011
La Roche College
2011
Rapt Therapeutics (United States)
2011
University of California, San Francisco
1997-2002
Abstract The tutorial introduces the readers to fundamentals of antibody pharmacokinetics (PK) in context drug development. Topics covered include an overview development, PK characteristics, and application PK/pharmacodynamics (PD) research development decision‐making. We also discuss general considerations for planning a nonclinical program describe types studies that should be performed during early monoclonal antibodies.
Antibody-drug conjugates (ADCs) are designed to combine the exquisite specificity of antibodies target tumor antigens with cytotoxic potency chemotherapeutic drugs. In addition general chemical stability linker, a thorough understanding relationship between ADC composition and biological disposition is necessary ensure that therapeutic window not compromised by altered pharmacokinetics (PK), tissue distribution, and/or potential organ toxicity. The six-transmembrane epithelial antigen...
Anti-HER2/CD3, a T-cell-dependent bispecific antibody (TDB) construct, induces T-cell-mediated cell death in cancer cells expressing HER2 by cross-linking tumor with CD3 on cytotoxic T cells, thereby creating functional cytolytic synapse. TDB design is very challenging process that requires consideration of multiple parameters. Although therapeutic strategy commonly driven striving for the highest attainable antigen-binding affinity, little known about how affinity each arm can affect...
Background: Antibody–drug conjugates (ADCs) are a new class of cancer therapeutics that deliver potent cytotoxins specifically to tumors minimize systemic toxicity. However, undesirable release covalently linked drugs in circulation can affect safety and efficacy. The objective this manuscript was propose assess the assays allow for characterization drug deconjugation plasma/serum. Results: ADCs three main conjugation platforms, via lysine, site-specific engineered cysteine or reduced...
Antibody-drug conjugates (ADC) selectively deliver a cytotoxic drug to cells expressing an accessible antigenic target. Here, we have appended monomethyl auristatin E (MMAE) antibody recognizing the SLC34A2 gene product NaPi2b, type II sodium-phosphate cotransporter, which is highly expressed on tumor surfaces of lung, ovary, and thyroid as well normal lung pneumocytes. This study evaluated its efficacy safety in preclinical studies.The anti-NaPi2b ADC was mouse ovarian non-small cell cancer...
Bispecific IgG production in single host cells has been a much sought-after goal to support the clinical development of these complex molecules. Current routes cell bispecific include engineering heavy chains for heterodimerization and redesign Fab arms selective pairing cognate light chains. Here, we describe novel designs facilitate arm assembly conjunction with previously described knobs-into-holes mutations preferential chain heterodimerization. The top pairing, namely variants v10 v11,...
TENB2, also known as tomoregulin or transmembrane protein with epidermal growth factor–like and 2 follistatin-like domains, is a proteoglycan overexpressed in human prostate tumors. This promising target for antimitotic monomethyl auristatin E (MMAE)–based antibody–drug conjugate (ADC) therapy. Nonlinear pharmacokinetics normal mice suggested that antigen expression tissues may contribute to targeted mediated disposition. We evaluated predosing strategy unconjugated antibody block ADC uptake...
This phase I trial assessed the safety, tolerability, and preliminary antitumor activity of lifastuzumab vedotin (LIFA), an antibody-drug conjugate anti-NaPi2b mAb (MNIB2126A) a potent antimitotic agent (monomethyl auristatin E).LIFA was administered to patients with non-small cell lung cancer (NSCLC) platinum-resistant ovarian (PROC), once every 3 weeks, by intravenous infusion. The starting dose 0.2 mg/kg in this 3+3 dose-escalation design, followed cohort expansion at recommended II...
The success of antibody-drug conjugates (ADCs) depends on the therapeutic window rendered by differential expression between normal and pathological tissues. ability to identify visualize target in tissues could reveal causes for target-mediated clearance observed pharmacokinetic characterization. TENB2 is a prostate cancer associated with progression poorly differentiated androgen-independent tumour types, ADCs specific are candidate therapeutics. objective this study was locate antigen...
The 4th World Antibody Drug Conjugate (WADC) Summit, organized by Hanson Wade was held on February 29‑March 1, 2012 in Frankfurt, Germany, which also the location for Summit Europe 2011. During one year between these meetings, antibody drug conjugates (ADCs) have confirmed their technological maturity and clinical efficacy oncology. Brentuximab vedotin (ADCETRISTM) gained approval US Food Administration August 2011 trastuzumab emtansine (T-DM1) impressive responses a large cohort of breast...
Antibody-drug conjugates (ADCs) are target-specific anticancer agents consisting of cytotoxic drugs covalently linked to a monoclonal antibody. The number ADCs in the clinic is growing, and therefore thorough characterization quantitative assays used measure ADC concentrations support pharmacokinetic, efficacy, safety studies increasing importance. Cytotoxic such as tubulin polymerization inhibiting auristatin, monomethyl auristatin E, have been conjugated antibodies via cleavable linkers...
Intracellular calcium is a universal second messenger that can serve as broadbased measure of receptor activity. Recent developments in multi-well plate fluorescence readers facilitate measurement intracellular free-calcium levels and reduce reliance on slower, more cumbersome or expensive data collection methods. In this report, we describe rapid sensitive method to assay ions human embryonic kidney (HEK293) Chinese hamster ovary (CHO) cells from plates using fluorometer equipped with...
// C. Andrew Boswell 1 , Daniela Bumbaca Yadav Eduardo E. Mundo 2 Shang-Fan Yu Jennifer Arca Lacap Aimee Fourie-O'Donohue Katherine R. Kozak Gregory Z. Ferl Crystal Zhang Jason Ho Sheila Ulufatu Leslie A. Khawli 3 and Kedan Lin 4 Genentech Research Early Development, South San Francisco, 94080 CA, USA Present address: Department of Safety Assessment, Nektar Therapeutics, 94158 Pathology Laboratory Medicine, Keck School Medicine USC, Los Angeles, 90033 Clinical Development US Operation,...
Miniaturization of immunoassays has numerous potential advantages over traditional ELISAs. Here we present a novel approach using patterned planar plates (PPPs). These 'wall-less' consist 16 × 24 array 2 mm diameter hydrophilic regions surrounded by hydrophobic polytetrafluoroethylene (PTFE) coating. Assays are performed adding μL droplets to the areas. overlaid with an immiscible mixture perfluorocarbon liquid (PFCL) that essentially eliminates evaporation. During wash steps, thin film PFCL...
Bispecific antibody production using single host cells has been a new advancement in the engineering field. We previously showed comparable vitro biological activity and vivo mouse pharmacokinetics (PK) for two novel cell variants (v10 v11) one traditional dual vitro-assembled anti-human epidermal growth factor receptor 2/CD3 T-cell dependent bispecific (TDB) antibodies. Here, we extended our previous work to assess cell-produced of TDB against FcRH5, B-cell lineage marker expressed on...
5020 Background: Six-transmembrane epithelial antigen of the prostate-1 (STEAP1) protein is a cell-surface overexpressed in human prostate cancers. The ADC DSTP3086S contains humanized IgG1 anti-STEAP1 monoclonal antibody linked to potent anti-mitotic agent MMAE. Methods: This study evaluated safety, pharmacokinetics, and pharmacodynamic activity intravenous (0.3-2.8 mg/kg) given every 3 weeks (q3w) pts with CRPC. A traditional 3+3 design was used determine maximum-tolerated dose, followed...
2507 Background: NaPi2b (SLC34A2) is a multi-transmembrane, sodium-dependent phosphate transporter expressed in non-squamous NSCLC and non-mucinous OC. DNIB0600A an ADC consisting of humanized IgG1 anti-NaPi2b monoclonal antibody anti-mitotic agent, MMAE, that shows anti-proliferative activity xenograft models. Methods: This study evaluated safety, pharmacokinetics, pharmacodynamics (0.2-2.8 mg/kg) given every 3 weeks (q3w) to pts with or A traditional 3+3 design was used for dose escalation...