A5062010822- interferon and immune responses
- Pancreatic and Hepatic Oncology Research
- Cytokine Signaling Pathways and Interactions
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Virus-based gene therapy research
- Occupational and environmental lung diseases
- Sarcoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- CAR-T cell therapy research
- Neuroendocrine Tumor Research Advances
- Multiple Myeloma Research and Treatments
- Animal Virus Infections Studies
- Virology and Viral Diseases
- Single-cell and spatial transcriptomics
- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Cancer Cells and Metastasis
- Monoclonal and Polyclonal Antibodies Research
- Pancreatitis Pathology and Treatment
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
Weatherford College
2023
Aduro BioTech (United States)
2015-2022
Stanford University
2012-2017
Novartis (Italy)
2013
Newron Pharmaceuticals (Italy)
2013
VA Palo Alto Health Care System
2012
Johns Hopkins University
2005-2008
Johns Hopkins Medicine
2008
Vical (United States)
2008
Novartis (United States)
2008
Abstract Purpose: This phase I study assessed the safety, pharmacokinetics (PKs), and efficacy of MIW815 (ADU-S100), a novel synthetic cyclic dinucleotide that activates stimulator IFN genes (STING) pathway, in patients with advanced/metastatic cancers. Patients Methods: (n = 47) received weekly i.t. injections MIW815, 50 to 6,400 μg, on 3-weeks-on/1-week-off schedule. Results: A maximum tolerated dose was not reached. Most common treatment-related adverse events were pyrexia (17%), chills,...
2507 Background: MIW815 (ADU-S100) is a novel synthetic cyclic dinucleotide that activates the STimulator of INterferon Genes (STING) pathway impacting tumor cells, microenvironment, vasculature, tumor-associated fibroblasts, and priming APC CD8+ T cells. Spartalizumab humanized IgG4 mAb blocks binding PD-1 to PD-L1/2. Preclinical data support synergistic antitumor effects when combined with checkpoint inhibitors. Methods: In this Phase Ib dose escalation study, pts advanced/metastatic solid...
Abstract Purpose: The stimulator of IFN genes (STING) is a transmembrane protein that plays role in the immune response to tumors. Single-agent STING agonist MIW815 (ADU-S100) has demonstrated activation but limited antitumor activity. This phase Ib, multicenter, dose-escalation study assessed safety and tolerability plus spartalizumab (PDR001), humanized IgG4 antibody against PD-1, 106 patients with advanced solid tumors or lymphomas. Patients Methods: were treated weekly intratumoral...
Individual human VP4- and VP7-binding monoclonal antibodies mediate serotype cross-reactive neutralizing immunity to rotaviruses.
Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with poor prognosis. CRS-207 a live-attenuated
“Bulk” measurements of antiviral innate immune responses from pooled cells yield averaged signals and do not reveal underlying signaling heterogeneity in infected bystander single cells. We examined such the small intestine during rotavirus (RV) infection. Murine RV EW robustly activated type I IFNs several genes (IFN-stimulated genes) by bulk analysis, source induced primarily being hematopoietic Flow cytometry microfluidics-based single-cell multiplex RT-PCR allowed dissection IFN...
Measles remains a major worldwide problem partly because of difficulties with vaccination young infants. New vaccine strategies need to be safe and provide sustained protective immunity. We have developed Sindbis virus replicon particles that express the measles (MV) hemagglutinin (SIN-H) or fusion (SIN-F) proteins. In mice, SIN-H induced high-titered, dose-dependent, MV-neutralizing antibody after single vaccination. SIN-F, SIN-F combined, somewhat lower responses. To assess efficacy,...
BackgroundEndemic transmission of measles continues in many countries that have a high human immunodeficiency virus (HIV) burden. The effects HIV infection has on immune responses to and vaccine can impact elimination efforts. Assays measure antibody include the enzyme immunoassay (EIA), which measures immunoglobulin G (IgG) all (MV) proteins, plaque reduction neutralization (PRN) assay, hemagglutinin correlates with protection. Antibody avidity may affect neutralizing capacity...
345 Background: GVAX is composed of irradiated, allogeneic pancreatic cancer cells modified to express GM-CSF and induce broad tumor antigen responses. Low-dose cyclophosphamide (CY) administered with inhibit regulatory T cells. CRS-207 live, attenuated, double-deleted Listeria monocytogenes(LADD) engineered mesothelin. boosts cell responses against mesothelin stimulates innate adaptive immunity. In an earlier Phase 2 study in patients mPDA, CY/GVAX + resulted a significant improvement...
Introduction: Episiotomy is a frequent obstetric intervention during vaginal delivery, necessitating effective repair techniques to minimize complications and enhance recovery. Continuous interrupted suturing are widely used, but their comparative efficacy remains debated. This study evaluates the impact of these on wound healing, pain, complications, patient satisfaction. Method: A prospective was conducted over two years at Saraswathi Institute Medical Sciences, Hapur, involving 200 women...
Measles remains an important cause of death worldwide, and vaccinating individuals at earlier age could lead to better control the disease. However, persistence maternal antibody young affect quantity vaccine-induced neutralizing may also quality.Enzyme immunoassay was used analyze measles virus-specific IgG levels, avidity maturation, isotype changes, using serum samples from infants who received vaccine 6 months measles-mumps-rubella (MMR)-II 12 (n=26), 9 (n=48), or only MMR-II (n=27).The...
A measles virus vaccine for infants under 6 months of age would help control measles. DNA vaccines hold promise, but none has provided full protection from challenge. Codon-optimized plasmid DNAs encoding the hemagglutinin and fusion glycoproteins were formulated with cationic lipid-based adjuvant Vaxfectin. In mice, antibody gamma interferon (IFN-gamma) production increased by two- to threefold. macaques, juveniles vaccinated at 0 28 days 500 microg intradermally or 1 mg intramuscularly...
ABSTRACT Measles remains an important cause of vaccine-preventable child mortality. Development a low-cost, heat-stable vaccine for infants under the age 6 months could improve measles control by facilitating delivery at time other vaccines and closing window susceptibility prior to immunization 9 age. DNA hold promise development, but achieving protective levels antibody has been difficult there is incomplete understanding immunity. In current study, we evaluated use layered alphavirus...
The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival patients metastatic pancreatic cancer who were enrolled phase II randomized studies GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used simultaneously measure 38 surface or intracellular markers peripheral blood mononuclear cells obtained from a IIa...
29 Background: CRS-207 is a live, attenuated, double-deleted Listeria monocytogenes (LADD) engineered to stimulate immune response mesothelin. In phase I trial of 60 MPM patients, 34% subjects had tumor reduction (range -1 -47%) following 2 doses alone. KEYNOTE-028 pembro showed activity in PDL1+ (≥1% by IHC) MPM, with an objective rate (ORR) 20% (5/25) and stable disease 52% who failed or did not receive chemotherapy. Subsequent studies have shown similar results MPM. Results from...
261 Background: In a phase 2a randomized study, metastatic pancreatic ductal adenocarcinoma (PDA) patients treated sequentially with two vaccine-based immunotherapies showed extended overall survival (OS) tolerable side effects. Treatment included low-dose cyclophosphamide (CY) to inhibit T-regulatory cells prior GVAX, an irradiated GM-CSF-secreting allogeneic PDA cell vaccine, which activates broad antigenic response, followed by CRS-207, live-attenuated, mesothelin-expressing Listeria...
8012 Background: BION-1301 (BION) is first in class humanized monoclonal antibody directed against a proliferation-inducing ligand (APRIL) for treatment of relapsed/refractory (R/R) multiple myeloma (MM). APRIL secreted by cells the bone marrow (BM) niche binds to BCMA (B-Cell maturation antigen) and TACI (transmembrane activator CAML interactor) expressed on human MM drive their proliferation survival. In patients (pts) with MM, serum levels are elevated correlated promotion malignancy,...
7565 Background: MPM is an aggressive disease with poor prognosis and relatively refractory to currently available therapies. CRS-207 live-attenuated Listeria monocytogenes engineered express the tumor-associated antigen mesothelin. Stimulation of potent innate adaptive immunity by may act synergistically in combination chemotherapy that alters tumor environment be more susceptible immune-mediated killing. Methods: Eligible patients were chemotherapy-naïve unresectable MPM, good performance...
Antigen-specific memory B cells generate anamnestic responses and high affinity antibodies upon re-exposure to pathogens. Attempts isolate rare antigen-specific for in-depth functional analysis at the single-cell level have been hindered by lack of tools with adequate sensitivity. We applied two independent methods protein labeling sensitive specific ex vivo identification flow cytometry: stringently controlled amine labeling, sortagging, a novel method whereby single nucleophilic...