A5102959403- CAR-T cell therapy research
- Theology and Philosophy of Evil
- Viral Infectious Diseases and Gene Expression in Insects
- Christian Theology and Mission
- Neuroblastoma Research and Treatments
- Antibiotics Pharmacokinetics and Efficacy
- Biblical Studies and Interpretation
- Immune Cell Function and Interaction
- Web and Library Services
- Antifungal resistance and susceptibility
- Karl Barth and Christian Theology
- Immunotherapy and Immune Responses
- Medieval Literature and History
- Digital Humanities and Scholarship
- Glioma Diagnosis and Treatment
- Religion and Society Interactions
- Virus-based gene therapy research
- Reformation and Early Modern Christianity
- Historical and Architectural Studies
- Fungal Infections and Studies
- Augustinian Studies and Theology
- Nanowire Synthesis and Applications
- Archaeology and Historical Studies
- Antibiotic Resistance in Bacteria
- Religion, Ecology, and Ethics
Georgetown University
2022-2025
University of Liverpool
2013-2024
Georgetown University Medical Center
2024
Brigham Young University
2024
Biola University
2015-2023
Seattle Children's Hospital
2015-2023
Sana Biotechnology (United States)
2021-2023
MedStar Health
2023
University of Maryland, College Park
2022
Mayo Clinic in Florida
2022
Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed B7-H3-specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), first-in-human phase I trial administering repeated locoregional CAR cells to children with recurrent/refractory CNS tumors DIPG. Here, report the results of first three...
Chimeric antigen receptor (CAR) development is biased toward selecting constructs that elicit the highest magnitude of T-cell functional outputs. Here, we show components CAR extracellular spacer and cytoplasmic signaling domain modulate, in a cooperative manner, CD8(+)CTL activation for tumor-cell cytolysis cytokine secretion. Unexpectedly, generate vitro activity, either by length tuning or addition modules, exhibit attenuated antitumor potency vivo, whereas CARs tuned moderate outputs...
The aim of this study was to improve the understanding pharmacokinetic-pharmacodynamic relationships fosfomycin against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains that have different MICs. Our methods included use a hollow fiber infection model with three clinical ESBL-producing E. strains. Human pharmacokinetic profiles were simulated over 4 days. Preliminary studies conducted determine dose ranges, including ranges suppressed development drug-resistant...
Abstract Purpose: The identification and vetting of cell surface tumor-restricted epitopes for chimeric antigen receptor (CAR)–redirected T-cell immunotherapy is the subject intensive investigation. We have focused on CD171 (L1-CAM), an abundant molecule neuroblastomas and, specifically, glycosylation-dependent tumor-specific epitope recognized by CE7 monoclonal antibody. Experimental Design: expression was assessed IHC using mAb in tumor microarrays primary, metastatic, recurrent...
Targeting solid tumor antigens with chimeric antigen receptor (CAR) T cell therapy requires specificity and tolerance toward variability in expression levels. Given the relative paucity of unique surface proteins on cells for CAR targeting, we have focused identifying tumor-specific epitopes that arise as a consequence target protein posttranslational modification. We designed using mAb806-based binder, which recognizes untethered EGFR. The mAb806 epitope is also exposed EGFRvIII variant...
Cryptococcal meningitis is a lethal disease with few treatment options. The incidence remains high and intricately linked the HIV/AIDS epidemic. In many parts of world, fluconazole only agent that available for initial cryptococcal despite considerable evidence it associated suboptimal microbiological clinical outcomes. Fluconazole has fungistatic mode action: predominantly inhibits growth rather than causing fungal killing. Our work shows pattern activity caused by emergence resistance in...
F901318 is an antifungal agent with a novel mechanism of action and potent activity against Aspergillus spp. An understanding the pharmacodynamics (PD) required for selection effective regimens study in phase II III clinical trials. Neutropenic murine rabbit models invasive pulmonary aspergillosis were used. The primary PD endpoint was serum galactomannan. relationships between drug exposure impacts dose fractionation on galactomannan, survival, histopathology determined. results benchmarked...
ABSTRACT Triazoles are first-line agents for treating aspergillosis. The prevalence of azole resistance in Aspergillus fumigatus is increasing, and cross-resistance a growing concern. In this study, the susceptibilities 40 A. clinical isolates were tested by using CLSI method with amphotericin B, itraconazole, voriconazole, posaconazole, new triazole isavuconazole. Isavuconazole MICs higher strains reduced to other triazoles, mirroring changes voriconazole susceptibility. differed depending...
Aspergillus flavus is one of the most common agents invasive aspergillosis and associated with high mortality. The orotomides are a new class antifungal novel mechanism action. An understanding pharmacodynamics (PD) lead compound F901318 required to plan safe effective regimens for clinical use.The pharmacokinetics (PK) PD were evaluated by developing in vitro vivo models fungal sinusitis. Galactomannan was used as pharmacodynamic endpoint all models. Mathematical PK-PD describe...
Chimeric antigen receptor (CAR)-T cell therapy has transformed pediatric oncology by producing high remission rates and durable responses in CD19+ B-cell malignancies. This scenario is ideal as CD19 expression homogeneous human blood provides a favorable environment for CAR-T cells to thrive destroy cancer (along with normal B cells). Yet, therapies solid tumors remain challenged fewer tumor targets poor performances hostile microenvironment. For acute myeloid leukemia childhood such...
Chimeric antigen receptor (CAR)-T cell immunotherapy is a novel treatment that genetically modifies the patients' own T cells to target and kill malignant cells. However, identification of tumour-specific antigens expressed on multiple solid cancer types, remains major challenge. P2X purinoceptor 7 (P2X7) surface ATP gated cation channel, dysfunctional version P2X7, named nfP2X7, has been identified from tissues, while being undetectable healthy We present prototype -human CAR-T construct...
The overall study aim was to identify the relevant preclinical teicoplanin pharmacokinetic (PK)/pharmacodynamic (PD) indices predict efficacy and suppression of resistance in MRSA infection.A hollow-fibre infection model a neutropenic murine thigh were developed. PK/PD data generated modelled using non-parametric population modelling approach with Pmetrics. posterior Bayesian estimates derived used exposure-effect relationships. Monte Carlo simulations from previously developed PK models...
Current therapeutic options for cryptococcal meningitis are limited by toxicity, global supply, and emergence of resistance. There is an urgent need to develop additional antifungal agents that fungicidal within the central nervous system preferably orally bioavailable. The benzimidazoles have broad-spectrum antiparasitic activity but also in vitro includes Cryptococcus neoformans Flubendazole (a benzimidazole) has been reformulated Janssen Pharmaceutica as amorphous solid drug...
CoNS are the most common cause of neonatal late-onset sepsis. Information on vancomycin pharmacokinetics/pharmacodynamics against is limited. The aim this study was to characterize pharmacokinetic/pharmacodynamic relationships for and investigate optimal dosage regimens. A hollow fibre a novel rabbit model central line-associated bloodstream infections were developed. results then bridged neonates by use population pharmacokinetic techniques Monte Carlo simulations. There dose-dependent...
Tebipenem pivoxil HBr (TBPM-PI-HBr) is a novel orally bioavailable carbapenem. The active moiety tebipenem. licensed for use in Japan children with ear, nose, and throat infections respiratory infections. salt was designed to improve drug substance product properties, including stability. TBPM-PI-HBr now being developed as an agent the treatment of complicated urinary tract (cUTI) adults. pharmacokinetics-pharmacodynamics tebipenem were studied well-characterized neutropenic murine thigh...
ABSTRACT Objective This study evaluated the safety and efficacy of isoproterenol administration as an adjunct for achievement target heart rate (HR) during dobutamine stress echocardiography (DSE). Background In DSE, optimal accuracy is achieved when a HR 85% maximal predicted (MPHR) attained. Although rarely studied, intravenous has been used therapy to atropine increase chronotropic response pharmacologic testing. Methods We identified 5569 DSE studies which 264 received at MedStar...
Abstract The advent of excimer laser coronary atherectomy (ELCA) nearly four decades ago heralded a novel way to treat complex lesions, both and peripheral, which were previously untraversable thus untreatable. These lesions include heavily calcified ostial bifurcation chronic total occlusions, in‐stent restenosis (including stent underexpansion), degenerative saphenous vein grafts. We discuss the technology ELCA, its indications, applications, complications, suggest “MAXCon ELCA” technique...
Cryptococcal meningoencephalitis is a rapidly lethal infection in immunocompromised patients. Induction regimens are usually administered for 2 weeks. The shortest effective period of induction therapy with liposomal amphotericin B (LAMB) unknown. pharmacodynamics LAMB were studied murine and rabbit models cryptococcal meningoencephalitis. concentrations the plasma brains mice measured using high-performance liquid chromatography (HPLC). Histopathological changes determined. penetration into...
Highlights•CD14+ depletion allows T cell expansion from cryopreserved G-CSF-stimulated peripheral blood stem cells (PBSCs).•Naïve and central memory precursors are present in PBSC units.•Chimeric antigen receptor (CAR-T) generated units exhibit antitumor activity.•Cryopreserved can serve as an alternative source for CAR-T products.•Use of stored apheresis extend the options heavily treated patients.ABSTRACTCytotoxic chemotherapy radiation render lymphocyte repertoires qualitatively...