A5084243027- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Nitric Oxide and Endothelin Effects
- Toxin Mechanisms and Immunotoxins
- Cancer Research and Treatments
- Glaucoma and retinal disorders
- HIV Research and Treatment
- Advanced biosensing and bioanalysis techniques
- Cytokine Signaling Pathways and Interactions
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Lymphoma Diagnosis and Treatment
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Luminescence and Fluorescent Materials
- Chronic Lymphocytic Leukemia Research
- Biosensors and Analytical Detection
- RNA Interference and Gene Delivery
- Immunodeficiency and Autoimmune Disorders
- Ophthalmology and Eye Disorders
Arcturus Therapeutics (United States)
2024
Massachusetts Institute of Technology
2017-2023
Ragon Institute of MGH, MIT and Harvard
2012-2023
Imperial College London
2012-2021
Kensington Health
2019
University of California, Los Angeles
2018
Duke University
2014-2017
Marin Endocrine Care and Research
2016
Kaiser Foundation Hospital
2014
University of Arizona
2012
Chimeric antigen receptor-T cell (CAR-T) therapy has been effective in the treatment of hematologic malignancies, but it shown limited efficacy against solid tumors. Here we demonstrate an approach to enhancing CAR-T function tumors by directly vaccine-boosting donor cells through their chimeric receptor vivo. We designed amphiphile ligands (amph-ligands) that, upon injection, trafficked lymph nodes and decorated surfaces antigen-presenting cells, thereby priming CAR-Ts native node...
In vaccine design, antigens are often arrayed in a multivalent nanoparticle form, but vivo mechanisms underlying the enhanced immunity elicited by such vaccines remain poorly understood. We compared fates of two different heavily glycosylated HIV antigens, gp120-derived mini-protein and large, stabilized envelope trimer, protein or "free" forms after primary immunization. Unlike monomeric nanoparticles were rapidly shuttled to follicular dendritic cell (FDC) network then concentrated...
Minimally invasive technologies that can sample and detect cell-free nucleic acid biomarkers from liquid biopsies have recently emerged as clinically useful for early diagnosis of a broad range pathologies, including cancer. Although blood has so far been the most commonly interrogated bodily fluid, skin interstitial fluid mostly overlooked despite containing same variety molecular originating cells surrounding capillaries. Emerging to this in pain-free minimally-invasive manner often take...
To combat the HIV epidemic and emerging threats such as SARS-CoV-2, immunization strategies are needed that elicit protection at mucosal portals of pathogen entry. Immunization directly through airway surfaces is effective in driving immunity, but poor vaccine uptake across mucus epithelial lining a limitation. The major blood protein albumin constitutively transcytosed bidirectionally epithelium interactions with neonatal Fc receptors (FcRn). Exploiting this biology, here, we demonstrate...
An adjuvant composed of saponin and a TLR4 agonist acts by enhancing lymph flow antigen entry into nodes.
Elevated intraocular pressure (IOP) is the main risk factor for glaucoma. Exogenous nitric oxide (NO) decreases IOP by increasing outflow facility, but whether endogenous NO production contributes to physiological regulation of facility unclear. Outflow was measured pressure-controlled perfusion in ex vivo eyes from C57BL/6 wild-type (WT) or transgenic mice expressing human endothelial synthase (eNOS) fused green fluorescent protein (GFP) superimposed on endogenously expressed murine eNOS...
Nitric oxide (NO) is able to lower intraocular pressure (IOP); however, its therapeutic effects on outflow physiology are location- and dose-dependent. A NO delivery platform that directly targets the resistance-generating region of conventional pathway locally liberates a controlled dose reported. An increase in facility (decrease IOP) demonstrated mouse model. Glaucoma second leading cause irreversible blindness affects more than 60 million people worldwide. Elevated (IOP) primary risk...
Aqueous humor filtration in the trabecular meshwork is believed to be non-uniform or "segmental" such that only a fraction of filtration-active at any given instant. The goal was quantify human and determine how patterns change with outflow facility intraocular pressure (IOP).Six pair enucleated eyes were perfused fluorescent tracer microspheres (0.2 μm) 7 30 mmHg. Tracer imaged over "macro-scale" (0.1-10 mm) using epifluorescence microscopy "micro-scale" (10-100 confocal microscopy....
Vascular endothelial growth factor (VEGF) regulates microvascular permeability, and the permeability of Schlemm's canal (SC) endothelium influences conventional aqueous humor outflow. We hypothesize that VEGF signaling outflow facility.We measured facility (C) in enucleated mouse eyes perfused with VEGF-A164a, VEGF-A165b, VEGF-D, or inhibitors to receptor 2 (VEGFR-2). monitored VEGF-A secretion from human trabecular meshwork (TM) cells by ELISA after 24 hours static culture cyclic stretch....
Purpose: We assess the effect of intravitreal anti-VEGF injections on tonographic outflow facility. Methods: Patients with age-related macular degeneration who had received unilateral were recruited into two groups, those ≤10 and ≥20 total injections. Intraocular pressure facility injected uninjected fellow eyes measured compared between groups. Risk factors for development reduced also assessed. Results: Outflow was 12% lower in patients injections, to contralateral (P = 0.02). In contrast,...
CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, mucin 1 targeted-dendritic cell (DC) treatment as maintenance therapy to patients with epithelial ovarian cancer (EOC).Patients (n = 56) in first (CR1) or second clinical remission (CR2) were randomized (1:1) standard care (SOC) observation CVac treatment. Ten doses administered over 56 weeks. Both groups followed for progression-free survival (PFS) overall (OS).Fifty-six...
Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular the liver, during acute stage of disease. While excessive liver can lead to more severe fibrosis and circulatory impairment chronically infected host. However, exact mechanism hepatic granuloma formation has remained obscure. In this study, we for first time showed that follicular helper T (Tfh) cells recruited upregulate injury S....
Coanchoring a SARS-CoV-2 immunogen and molecular adjuvants to alum extends vaccine kinetics amplifies humoral immunity.
The anti-programmed cell death-1 (PD-1) and death ligand-1 (PD-L1) immunotherapies have shown exceptional activity in many cancers. However, these can also result diverse adverse cutaneous eruptions that need to be better characterized for ongoing management. objective was provide clinical histopathologic descriptions of the variety events seen patients who received anti-PD-1/PD-L1 treatment discuss their management.Patients with advanced cancers trials at University California Los Angeles...
Abstract Oligonucleotide‐templated reactions are valuable tools for nucleic acid sensing both in vitro and vivo. They typically carried out under conditions that make any reaction the absence of template highly unfavorable (most commonly by using a low concentration reactants), which has negative impact on detection sensitivity. Herein, we report novel platform fluorogenic oligonucleotide‐templated between peptide probes embedded within permeable agarose alginate hydrogels. We demonstrate...
Low-cost detection of miRNA biomarkers from maternal blood is achieved via a highly sequence-specific templated reaction on nitrocellulose paper strips to enable early prediction preterm birth in minimally invasive manner.
Abstract In the ongoing effort to develop a vaccine against HIV, approaches that promote strong germinal center (GC) responses may be critical enable selection and affinity maturation of rare B cell clones capable evolving produce broadly neutralizing antibodies. We previously demonstrated an approach for enhancing GC overall humoral immunity elicited by alum-adjuvanted protein immunization via use phosphoserine (pSer) peptide-tagged immunogens stably anchor alum particles ligand exchange...
Abstract Despite clinical evidence of antitumor activity, the development cytokine therapies has been hampered by a narrow therapeutic window and limited response rates. Two cytokines high interest for are interleukin 2 (IL2) 12 (IL12), which potently synergize to promote activation proliferation T cells NK cells. However, only approved human IL2 therapy, Proleukin, is rarely used in clinic due systemic toxicities, no IL12 product date severe dose-limiting toxicities. Here, we describe...
<div>Abstract<p>Despite clinical evidence of antitumor activity, the development cytokine therapies has been hampered by a narrow therapeutic window and limited response rates. Two cytokines high interest for are interleukin 2 (IL2) 12 (IL12), which potently synergize to promote activation proliferation T cells NK cells. However, only approved human IL2 therapy, Proleukin, is rarely used in clinic due systemic toxicities, no IL12 product date severe dose-limiting toxicities....
Of critical importance in drug delivery and tissue engineering applications is the degradabilty of implanted polymeric materials. The use peptide-derived cross-linkers hydrogel design a valuable approach by which carriers can be endowed with enzymatic degradability predictable, "programmable" fashion. solid-phase synthesis strategy described herein allows for an expeditious, flexible bis-acrylamide-derivatized peptides complex modifications, as exemplified incorporation fluorophore quencher...
Nitric oxide (NO) is a free radical signaling molecule that plays crucial role in modulating physiological homeostasis across multiple biological systems. NO dysregulation linked to the pathogenesis of diseases; therefore, its quantification important for understanding pathophysiological processes. The detection challenging, typically limited by reactive nature and short half‐life. Additionally, presence interfering analytes accessibility fluids native tissues make measurement technically...
Protein antigens are often combined with aluminum hydroxide (alum), the most commonly used adjuvant in licensed vaccines; yet immunogenicity of alum-adjuvanted vaccines leaves much room for improvement. Here, authors demonstrate a strategy codelivering an immunostimulatory cytokine, interleukin IL-21, engineered outer domain (eOD) human immunodeficiency virus gp120 Env immunogen eOD, bound together to alum bolster humoral immune response. In this approach, and cytokine co-anchored particles...