A5080095501- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Glycosylation and Glycoproteins Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Influenza Virus Research Studies
- Biosimilars and Bioanalytical Methods
- Lymphoma Diagnosis and Treatment
- Galectins and Cancer Biology
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Chronic Lymphocytic Leukemia Research
- Immune cells in cancer
- Radiopharmaceutical Chemistry and Applications
- GDF15 and Related Biomarkers
- Immune Cell Function and Interaction
- Heme Oxygenase-1 and Carbon Monoxide
- Hematopoietic Stem Cell Transplantation
- Animal testing and alternatives
- Chemical Synthesis and Analysis
- Folate and B Vitamins Research
- Spectroscopy Techniques in Biomedical and Chemical Research
- Redox biology and oxidative stress
Seagen (United States)
2015-2024
Pfizer (United States)
2024
University of Washington
2007-2008
Washington State University
2003-2007
Lewis Clark State College
2001
Abstract The contribution of environmental factors is important as we consider reasons that underlie differential susceptibility to influenza virus. Aryl hydrocarbon receptor (AhR) activation by the pollutant dioxin during virus infection decreases survival, which correlates with a 4-fold increase in pulmonary IFN-γ levels. We report here majority IFN-γ-producing cells lung are neutrophils and macrophages not lymphocytes, elevated associated increased inducible NO synthase (iNOS) Moreover,...
Abstract Nonclinical safety and pharmacokinetic data for monomethyl auristatin E (MMAE) 14 vedotin antibody–drug conjugates (ADC) were evaluated to determine patterns of toxicity, consistency results, species differences between rats monkeys. Most nonclinical toxicities antigen-independent, common across ADCs, included hematologic, lymphoid, reproductive toxicity related MMAE pharmacology. Hematologic was the dose-limiting (DLT) or predominant majority ADCs in both species. Tissue expression...
3074 Background: SEA-CD40 is a non-fucosylated, humanized IgG1 monoclonal antibody directed against human CD40. It derived from dacetuzumab, previously developed for B-lineage malignancies. Antibody glycosylation essential Fc receptor-mediated activity and nonfucosylated antibodies may show improved efficacy via increased binding to FcγRIIIa (CD16). Methods: Enhanced functionality of was determined through binding, immune activation, induction antigen-specific T-cells Results: While the...
Abstract Hydrogen peroxide (H 2 O ) can cause single strand DNA breaks (ssDNA) in cells when the mechanisms normally place to reduce it are overwhelmed. Such include catalase, glutathione peroxidases (GPx), and peroxiredoxins. The relative importance of these enzymes H reduction varies with cell tissue type. role GPx cofactor (GSH) oxidative defense be further understood by modulating its synthesis. first rate‐limiting enzyme GSH synthesis is glutamate‐cysteine ligase (GCL), which has a...
Abstract SEA-CD40 is a non-fucosylated, humanized IgG1 monoclonal antibody directed against human CD40, co-stimulatory receptor of the TNF superfamily. derived from dacetuzumab, previously developed and studied for B-lineage malignancies. Glycosylation Fc essential receptor-mediated activity non-fucosylated antibodies show improved efficacy, particularly via increased binding to low affinity FcγRIIIa. Enhanced functionality was determined through FcγRIIIa affinity, antibody-dependent...
Abstract CD40 is a co-stimulatory receptor of the TNF superfamily expressed on antigen presenting cells (APCs). Antibodies targeting may have therapeutic benefit via multiple mechanisms including innate immune activation that can support generation antigen-specific, antitumor T cell responses, and binding to CD40-expressing cancer leading antibody-mediated target killing. Multiple CD40-directed antibodies are in clinical development differ by immunoglobulin isotype, affinity CD40,...
Antibody effector functions including antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) are mediated through the interaction of antibody Fc region with Fcγ receptors present on immune cells. Several approaches have been used to modulate Fc-Fcγ interactions goal driving an effective antitumor response, point mutations glycan modifications. However, robust antibody-Fcγ engagement cell binding Fc-enhanced antibodies in periphery can lead unwanted induction systemic...
<div>Abstract<p>Nonclinical safety and pharmacokinetic data for monomethyl auristatin E (MMAE) 14 vedotin antibody–drug conjugates (ADC) were evaluated to determine patterns of toxicity, consistency results, species differences between rats monkeys. Most nonclinical toxicities antigen-independent, common across ADCs, included hematologic, lymphoid, reproductive toxicity related MMAE pharmacology. Hematologic was the dose-limiting (DLT) or predominant majority ADCs in both...
<p>Supplementary Figure 2. Reproductive toxicity with vedotin ADCs in cynomolgus monkeys.</p>
<p>Supplementary Figure 1. Hematopoietic and lymphoid tissue toxicity in cynomolgus monkeys administered a vedotin ADC or MMAE.</p>
Abstract SEA-TGT is a human nonfucosylated monoclonal antibody (mAb) targeting the T cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) protein. TIGIT an immunoregulatory receptor expressed on activated memory cells, Tregs, NK cells. binding to CD155 CD112 tumor cells drives inhibitory signal resulting in decreased functionality. has been reported release these signals, drive Treg depletion, augment CD8+ generation, promote anti-tumor responses. SGNTGT-001 (NCT04254107)...
Abstract Carcinoembryonic antigen cell adhesion molecule 5, CEACAM5, is a glycosylphosphatidylinositol-anchored glycoprotein highly expressed on the surface of several epithelial tumors. CEACAM5 in virtually all colorectal cancer, ~90% which to high levels while normal tissue expression limited. The prevalence tumor cells prompted us develop an investigational anti-CEACAM5 antibody-drug conjugate (ADC) for potential treatment CRC patients. We developed novel ADC, by conjugating antibody with...
Abstract SEA-CD40 is a non-fucosylated, humanized IgG1 monoclonal antibody directed against human CD40, co-stimulatory receptor of the TNF superfamily. The consequence enhanced SEA-CD40/FcγRIIIa binding potent immune stimulatory activity. CD40 ligation induces multiple pathways; to pave road for identification specific activity signature in clinical setting, vitro preclinical assays were developed monitor modulatory SEA-CD40. Human PBMCs stimulated with increasing concentrations assessed...
<h3>Background</h3> PD-1/PD-L1 immune checkpoint inhibitors have transformed oncology, but a significant unmet need persists for patients with relapsed/refractory tumors following treatment. PD-L1 is expressed in across broad spectrum of tumor types and displays limited normal tissue expression, highlighting the potential as target antibody-drug conjugates (ADCs) addition to its role an checkpoint. SGN-PDL1V PD-L1-directed ADC currently under preclinical investigation, which comprised...
Abstract Antibody-drug conjugates (ADCs) continue to emerge as effective therapeutics in a variety of oncology indications. Research on ADCs has revealed that the physicochemical properties drug-linker component can exert significant impact disposition ADCs, particularly at higher levels drug loading. We have recently reported (Nature Biotechnology 33, 733-735 (2015); Molecular Cancer Therapeutics, manuscript accepted) these be modulated through judicious incorporation small, discrete PEG...
<h3>Background</h3> CD40 is a co-stimulatory receptor of the TNF superfamily expressed on antigen presenting cells (APCs). Antibodies targeting may have antitumor therapeutic benefit by driving innate immune cell activation that supports generation antigen-specific T responses. Multiple CD40-directed antibodies are in clinical development both solid and hematologic indications differ according to immunoglobulin isotype, affinity CD40, differential FcγR-binding. SEA-CD40 an agonistic...
Abstract Modification of effector function has proven to be an effective modality for optimizing activity and tolerability therapeutic antibodies. Currently available methods modulate include the introduction point mutations in Fc region glycan engineering antibody. Here we present alternative complementary method tuning utilizing a conjugation-based approach. This methodology uses conjugation polyethylene glycol (PEG) native cysteines antibody impair FcγR binding antibodies innate immune...
Abstract Antibody-drug conjugates (ADCs) continue to emerge as effective therapeutics in a variety of oncology indications, with two agents currently approved and many more late-stage clinical trials. These ADCs employ drug-linkers that were developed years ago, are now recognized have properties may adversely impact the activity toxicology prepared them. Two such well appreciated reversibility maleimide-based drug conjugation, conjugation on pharmacokinetics ADC. We recently reported...