A5002004063- interferon and immune responses
- Neuroblastoma Research and Treatments
- Ubiquitin and proteasome pathways
- Radiopharmaceutical Chemistry and Applications
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Peptidase Inhibition and Analysis
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Nanoparticles: synthesis and applications
- Air Quality and Health Impacts
- Virus-based gene therapy research
- Asthma and respiratory diseases
- Advanced biosensing and bioanalysis techniques
- Inflammasome and immune disorders
- Nuclear Receptors and Signaling
- Biomedical Text Mining and Ontologies
- Autophagy in Disease and Therapy
- Nitric Oxide and Endothelin Effects
- Heme Oxygenase-1 and Carbon Monoxide
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Diamond Materials (United States)
2025
Mersana Therapeutics (United States)
2018-2024
Center for Environmental Health
2006-2021
University of Montana
2006-2021
Novartis (United States)
2017
Selecta Biosciences (United States)
2016
University of Kansas Medical Center
1996
Abstract Background Several properties of multi-walled carbon nanotubes (MWCNT) have the potential to affect their bioactivity. This study examined in vitro and vivo outcomes influence diameter, length, purification carboxylation ( testing only) MWCNT. Methods Three original ‘as received’ MWCNT that varied size (diameter length) were purified functionalized by carboxylation. The resulting characterized for cytotoxicity inflammasome activation using THP-1 cells primary alveolar macrophages...
Abstract Activating interferon responses with STING agonists (STINGa) is a current cancer immunotherapy strategy, and therapeutic modalities that enable tumor-targeted delivery via systemic administration could be beneficial. Here we demonstrate tumor cell-directed agonist antibody-drug-conjugates (STINGa ADCs) activate in cells myeloid induce anti-tumor innate immune vitro, vivo (in female mice), ex models. We show the STINGa ADCs are internalized into by Fcγ-receptor-I antigen-dependent...
Antibody-drug conjugates (ADC) achieve targeted drug delivery to a tumor and have demonstrated clinical success in many types. The activity safety profile of an ADC depends on its construction: antibody, payload, linker, conjugation method, as well the number payload drugs per antibody [drug-to-antibody ratio (DAR)]. To allow for optimization given target antigen, we developed Dolasynthen (DS), novel platform based auristatin hydroxypropylamide, that enables precise DAR-ranging site-specific...
The authors describe a 62-year-old woman with symptoms of major depression presumed to be secondary propranolol use. patient responded poorly imipramine; however, her cleared rapidly when atenolol was substituted for propranolol.
Abstract Purpose: Targeted tumor delivery may be required to potentiate the clinical benefit of innate immune modulators. The objective study was apply an antibody-drug conjugate approach STING agonism and develop a candidate. Methods: XMT-2056, HER2-directed STING-agonist (ADC), designed, built, tested in pharmacology toxicology studies. ADC compared benchmark intravenously administered agonist. Results: XMT-2056 achieved tumor-targeted agonist upon systemic administration mice induced...
<p>Figure S6. FVB/NJ immune competent mice bearing syngeneic mBR9013 subcutaneous tumors were intravenously administered anti-mouse PD-1 (clone RPM1-14) 10 mg/kg twice weekly for 3 weeks (red triangles). Each point represents the mean tumor volume and SEM (n=5).</p>
<p>Figure S5. A. PK profile of XMT-2056 in non-tumor bearing CB.17 SCID mice as a function total antibody (Total Ab) and conjugated drug concentrations plasma after single intravenous administration. Each line represents an individual animal (n=4). B. cynomolgus monkey during Q3W repeat-dose administration indicated by the black arrowheads. 1 male female were dosed; each data from one animal.</p>
<p>Figure S1. Characterization of XMT-2056</p>
<p>Figure S7. A. CB.17 SCID mice bearing subcutaneous JIMT-1 xenograft tumors were administered 3 weekly doses of XMT-2056, a combination non-binding control ADC and pertuzumab, or XMT-2056 pertuzumab. B. SNU-5 single dose ADC, ADCs intravenously while pertuzumab was intraperitoneally. Each point represents the mean tumor volume SEM (n=10).</p>
<p>Figure S8. A, B. BALB/c immune competent mice bearing syngeneic EMT-6-rHER2 tumors were treated with XMT-2056 surrogate ADC, anti-mouse PD-1 (Clone RPM1-14), non-binding control ADC in combination PD-1, or PD-1. The ADCs administered once while the mouse anti-PD-1 was twice weekly for 2 weeks as indicated by red triangles. A. Tumor volumes of individual mice, number complete responders (CR) indicated. Percent change body weight (BW). Each point represents mean BW and SEM (n=10).</p>
<p>Figure S2. A. STING mediated IRF3 activity of THP1 reporter cells expressing the indicated human STING1 haplotypes or knockout (KO) after treatment with agonist at doses. Each point represents mean and SD (n=2). B. Cytokine induction as measured by a multiplex Luminex assay from supernatants fresh white blood treated for 6 (IFN-β) 24 (CXCL10, IL-6, TNF-α) hours concentrations agonist. Bars represent value n=2 data points shown symbols. C. Structure HER2 extracellular domain showing...
<p>Figure S4. A. HER2 expression by IHC in SKOV3 xenograft tumors; scale bar, 20 µm. B. Percent changes body weights of tumor-bearing CB.17 SCID mice administered a single dose (black arrowhead) XMT-2056, non-binding control ADC, HT19, or STING agonist payload, 3 doses (orange the diABZI agonist. Each point represents mean change weight and SEM (n=10). C. Normalized counts for mouse mRNA human individual tumor cytokine/chemokines xenografts harvested 12 hours after treatment. SD (n=2)....
<p>Figure S3. A. Cancer cell death induced by XMT-2056, HT19 antibody, or non-binding control ADC, shown as percent viable SKBR3-NR (left) MDA-MB-175-VII-NR (right) cells in PBMC co-cultures (84 hr time point). Each point represents mean and SD (n=3). B. Cytokine induction HT19, ADC measured supernatants of (top) (bottom) (24 C. STING agonist payload monocultures MDA-MB-231-NR (n=3).</p>
<div>AbstractPurpose:<p>Targeted tumor delivery may be required to potentiate the clinical benefit of innate immune modulators. The objective study was apply an antibody–drug conjugate (ADC) approach STING agonism and develop a candidate.</p>Experimental Design:<p>XMT-2056, HER2-directed agonist ADC, designed, synthesized, tested in pharmacology toxicology studies. ADC compared with benchmark intravenously administered agonist.</p>Results:<p>XMT-2056...
Abstract STING pathway agonism has emerged as a potential therapeutic mechanism to stimulate an innate anti-tumor immune response. While in principle systemic administration of agonist would have many benefits, including the delivery all tumor lesions, such approach may be limited by toxicity. Antibody-drug conjugates (ADCs) constitute proven modality that is ideally suited enable without associated toxicity concerns via targeted strategy. Herein, we demonstrate systemically administered...
Abstract STING pathway agonism has emerged as a potential therapeutic mechanism to stimulate an innate anti-tumor immune response. However, the systemic administration of free agonist may be limited by toxicity, and broad biodistribution not ideal. Antibody-drug conjugates (ADCs) constitute proven modality that enables tumor-targeted delivery thus is ideally suited with reduced toxicity. To develop optimized STING-agonist ADC platform, we designed novel specifically tailored for use in ADC....
Abstract Natural Tregs are highly effective at inhibiting Th2 differentiation but restrictive in their ability to suppress airway inflammatory processes. nTregs prevent autoimmunity and modulate immune responses foreign antigens. CD4+Foxp3+ from DO11.10 mice were expanded ex vivo, effectiveness suppressing the development of lung responses, elicited by differentiated CD4+ T cells following antigen inhalation, was examined. Effector cells, when adoptively transferred into BALB/c that...
γδ T cells rapidly produce cytokines and represent a first line of defense against microbes other environmental insults at mucosal tissues are thus thought to play local immunoregulatory role. We show that allergic airway inflammation was associated with an increase in innate IL-17-producing (γδ-17) expressed the αEβ7 integrin were closely epithelium. Importantly, PGI(2) its receptor IP, which downregulated eosinophilic inflammation, promoted emergence these intraepithelial γδ-17 into...
Abstract Background A very pure multi-walled carbon nanotube (MWCNT) that was shown to have low toxicity in vitro, evaluated for lung and systemic effects distribution following inhalation exposure. Methods B6C3F1/N mice were exposed varying doses (0, 0.06, 0.2, 0.6 mg/m 3 ) of the (99.1% carbon) MWCNT by 30 days (excluding weekends). Ten last exposure, lungs spleen harvested processed histology immune cell population assessment. In addition, lavage cells fluid analyzed. Stimulated Raman...