A5025256316- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Glycosylation and Glycoproteins Research
- Radiopharmaceutical Chemistry and Applications
- Synthesis and properties of polymers
- Melanoma and MAPK Pathways
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Estrogen and related hormone effects
- Cancer Treatment and Pharmacology
- Synthesis and Biological Evaluation
- Cell Adhesion Molecules Research
- Potassium and Related Disorders
- Advanced biosensing and bioanalysis techniques
- Gold and Silver Nanoparticles Synthesis and Applications
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Biosensors and Analytical Detection
- Heparin-Induced Thrombocytopenia and Thrombosis
- Brazilian cultural history and politics
- CAR-T cell therapy research
- Biochemical and Structural Characterization
- Vasculitis and related conditions
- Medical Imaging Techniques and Applications
University of Illinois Urbana-Champaign
2020-2024
Seagen (United States)
2016-2023
Centre Hospitalier Universitaire de Bordeaux
2021
Oberlin College
2017
A quaternary ammonium-based drug-linker has been developed to expand the scope of antibody-drug conjugate (ADC) payloads include tertiary amines, a functional group commonly present in biologically active compounds. The linker strategy was exemplified with β-glucuronidase-cleavable auristatin E construct. found efficiently release free (AE) presence β-glucuronidase and provide ADCs that were highly stable plasma. Anti-CD30 conjugates comprised glucuronide-AE potent immunologically specific...
SGN-CD228A is an investigational antibody-drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. consists of humanized antibody, hL49, with high specificity and affinity for CD228 that stably conjugated 8 molecules the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via novel glucuronide linker. We performed comprehensive IHC studies, which corroborated published RNA sequencing data...
Although antibody-drug conjugates (ADCs) find increasing applications in cancer treatment, de novo or treatment-emergent resistance mechanisms may impair clinical benefit. Two that emerge under prolonged exposure include upregulation of transporter proteins confer multidrug (MDR+) and loss cognate antigen expression. New technologies circumvent these serve to extend the utility next-generation ADCs. Recently, we developed quaternary ammonium linker system expand scope conjugatable payloads...
Tubulysins have emerged in recent years as a compelling drug class for delivery to tumor cells via antibodies. The ability of this exert bystander activity while retaining potency against multidrug-resistant cell lines differentiates them from other microtubule-disrupting agents. Tubulysin M, synthetic analogue, has proven be active and well tolerated an antibody-drug conjugate (ADC) payload, but the liability being susceptible acetate hydrolysis at C11 position, leading attenuated potency....
Gold nanoparticles (AuNPs) and aptamers are compelling building blocks for analytical assays with desired attributes of selectivity sensitivity may theoretically form the basis instrument-free color-changing any target against which a DNA aptamer has been selected. However, proteins based on these components be subject to significant interferences from interaction nanoparticles. We found that three representative protein/aptamer systems-thrombin, apolipoprotein E, platelet-derived growth...
Abstract Background: Tucatinib is an orally administered, reversible, highly specific HER2 tyrosine kinase inhibitor recently approved by the FDA in combination with trastuzumab and capecitabine for adult patients advanced unresectable or metastatic HER2-positive breast cancer (mBC), including brain metastases, that have failed at least one anti-HER2 regimen setting. In a phase IB clinical trial, tucatinib HER2-targeted antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1) was well...
Abstract While antibody-drug conjugates (ADCs) find increasing application in cancer treatment regimens, de novo or treatment-emergent resistance mechanisms could impair clinical benefit. Two that emerge under continuous ADC exposure vitro include upregulation of transporters confer multidrug (MDR+) and loss cognate antigen expression. New technologies circumvent these may serve to extend the utility next generation ADCs. Recently, we developed quaternary ammonium linker system expand scope...
Abstract The recent clinical success of antibody-drug conjugates (ADCs) has spawned an increased effort to identify new technologies, and the development drug-linker chemistry is vital expand scope conjugatable payloads. tertiary amine functional group a common structural motif present in many bioactive compounds, including antimitotics auristatin tubulysin classes. Traditionally, conjugation amines required drug derivatization or modification remove N-alkyl group, thus creating readily...
<p>Antibody humanization, binding assays, conjugation, mass spec, additional in vivo details</p>
<p>Figures S1-S9</p>
<p>Figures S1-S9</p>
<div>Abstract<p>SGN-CD228A is an investigational antibody–drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. SGN-CD228A consists of humanized antibody, hL49, with high specificity and affinity for CD228 that stably conjugated 8 molecules the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via novel glucuronide linker. We performed comprehensive IHC studies, which...
<div>Abstract<p>SGN-CD228A is an investigational antibody–drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. SGN-CD228A consists of humanized antibody, hL49, with high specificity and affinity for CD228 that stably conjugated 8 molecules the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via novel glucuronide linker. We performed comprehensive IHC studies, which...
<p>Antibody humanization, binding assays, conjugation, mass spec, additional in vivo details</p>
<div>Abstract<p>A quaternary ammonium-based drug-linker has been developed to expand the scope of antibody–drug conjugate (ADC) payloads include tertiary amines, a functional group commonly present in biologically active compounds. The linker strategy was exemplified with β-glucuronidase–cleavable auristatin E construct. found efficiently release free (AE) presence β-glucuronidase and provide ADCs that were highly stable plasma. Anti-CD30 conjugates comprised glucuronide-AE...
<p>Figures S1-S9</p>
<p>Antibody humanization, binding assays, conjugation, mass spec, additional in vivo details</p>
<p>Experimental details for the chemical synthesis of drug-linkers.</p>
<p>Plasma stability of quaternary ammonium linker in rodent plasma.</p>
<p>Pharmacokinetic profile of clearance for three ADCs.</p>