A5024421938- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Oil Spill Detection and Mitigation
- Inflammatory Bowel Disease
- CAR-T cell therapy research
- Atmospheric and Environmental Gas Dynamics
- Biosimilars and Bioanalytical Methods
- Single-cell and spatial transcriptomics
- Microscopic Colitis
- Advanced Biosensing Techniques and Applications
- Cancer Genomics and Diagnostics
- Viral gastroenteritis research and epidemiology
- Salmonella and Campylobacter epidemiology
- Bacteriophages and microbial interactions
- Protein purification and stability
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Hydrology and Drought Analysis
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Water Quality and Resources Studies
- Cancer Mechanisms and Therapy
Clovis Oncology (United States)
2023
Takeda (United States)
2015-2021
Curis (United States)
2016-2019
Millennium Engineering and Integration (United States)
2008-2017
University of California San Francisco Medical Center
2017
Takeda (Japan)
2015
Johns Hopkins University
2006
University of Maryland, Baltimore
1999-2003
United States Geological Survey
1980
Vedolizumab, an anti-α(4)β(7) integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb concentrations have been associated greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help optimise dosing.To characterise pharmacokinetics UC CD, identify clinically relevant clearance, describe the...
Abstract Objective CCR2 is a chemokine receptor expressed by monocytes, macrophages, and subset of T cells. Its ligand, CCL2 (monocyte chemotactic protein 1), abundantly present in the synovium patients with rheumatoid arthritis (RA). Blocking prevents CCL2‐mediated chemotaxis vitro modulates animal models RA. In this study we examined effects blockade on synovial inflammation Methods The was designed as phase IIa clinical trial human blocking antibody (MLN1202) active Thirty‐two received 3...
ABSTRACT Salmonella enterica serovar Typhi strain CVD 908- htrA is a live attenuated which may be useful as an improved oral typhoid vaccine and vector for cloned genes of other pathogens. We conducted phase 2 trial in 80 healthy adults received one two dosage levels double-blind, placebo-controlled, crossover study. There were no differences the rates side effects among volunteers who high-dose (4.5 × 10 8 CFU), lower-dose (5 7 or placebo 21 days after vaccination, although recipients (8%)...
The cytokine production patterns of human peripheral blood mononuclear cells (PBMC) in response to Salmonella typhi flagella (STF) were examined culture supernatants PBMC stimulated with STF. Consistent previous findings volunteers vaccinated aroC aroD deletion mutants S. typhi, from immunized the licensed live Ty21a vaccine secreted gamma interferon following exposure Stimulation STF induced rapid de novo synthesis tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta),...
Type 1 cell-mediated immunity might play an important role in protection from typhoid fever. We evaluated whether immunization with Salmonella enterica serovar Typhi (S. Typhi) strain CVD 908-htrA (a Delta aroC aroD htrA mutant), a leading live oral vaccine candidate, elicits specific CD4(+) and CD8(+) S. immune responses. Potent CTL responses IFN-gamma secretion by T cells were detected following high (4.5 x 10(8) CFU) low (5 10(7) dosages. Typhi-specific observed six of eight vaccinees...
Abstract Background: AU-007 is a computationally designed mAb that binds interleukin-2 (IL-2) on its CD25 binding epitope. AU-007-bound IL-2 cannot bind trimeric (CD25, CD122, CD132) receptors (IL-2R) regulatory T cells (Tregs), vascular endothelium, or eosinophils, but IL-2’s to dimeric (CD122, IL-2R effector (T eff) and NK unhindered. thus redirects towards eff cell activation, while diminishing Treg activation leak, generated from expansion, converting Treg-mediated autoinhibitory loop...
Increasingly, commercial immunoassay kits are used to support drug discovery and development. Longitudinally consistent kit performance is crucial, but the degree which reagents characterized by manufacturers not standardized, nor approaches users adapt them evaluate their through validation prior use. These factors can negatively impact data quality. This paper offers a systematic approach assessment, method adaptation of for quantification biomarkers in development, expanding upon previous...
A key function of monocytes/macrophages (Mphi) is to present antigens T cells. However, upon interaction with bacteria, Mphi lose their ability effectively soluble antigens. This functional loss was associated alterations in the expression adhesion molecules and CD14 a reduction uptake antigen. Recently, we have demonstrated that Salmonella typhi flagella (STF) markedly decrease are potent inducers proinflammatory cytokine production by human peripheral blood mononuclear cells (hPBMC). In...
The U.S. Geological Survey has developed an oilspill risk analysis model to aid in estimating the environmental hazards of developing oil resources Outer Continental Shelf (OCS) lease areas. large, computerized analyzes probability spill occurrence, as well likely paths or trajectories spills relation locations recreational and biological which may be vulnerable. analytical methodology can easily incorporate estimates weathering rates , slick dispersion, possible mitigating effects cleanup....
Background The transmembrane receptor guanylate cyclase-C (GCC) has been found to be expressed in colorectal cancers. However, limited data are available on GCC protein expression non-colorectal gastrointestinal tumors and few studies have reported whether was consistently preserved synchronous primary metastatic cancer tissues. Methods status assessed by immunohistochemistry tumor specimens from individuals (n = 627) with tumors, including esophageal 130), gastric 276), pancreatic 136), 85)...
Abstract Vedolizumab immunogenicity has been assessed using an enzyme-linked immunosorbent assay (ELISA) with a ~ 0.5 μg/mL drug interference, which may underestimate on-drug immunogenicity. We aimed to compare results between ELISA and the new drug-tolerant electrochemiluminescence (ECL) (and two versions of neutralizing assays, drug-sensitive versus drug-tolerant). The ECL tolerance is 100 times higher than that (≥ 50 vs. 500 ng/mL positive control), sensitivity < 5 for both assays. was...
Abstract Patients in the GEMINI 1 or 2 study (NCT00790933; Eudra CT2008‐002784‐14) with ulcerative colitis Crohn disease had low immunogenicity rates after vedolizumab treatment for up to 52 weeks. We report from long‐term safety (LTS) using a new drug‐tolerant electrochemiluminescence assay, including analyses patients who received continuous induction and maintenance long term safety, placebo followed by re‐treatment (treatment interruption). were enrolled 1, 2, 3, as de novo...
The sharing of clinical trial data and biomarker sets among the scientific community, whether originates from pharmaceutical companies or academic institutions, is critical importance to enable development new improved cancer immunotherapy modalities. Through sharing, a better understanding current therapies in terms their efficacy, safety profiles can be achieved. However, these involves number stakeholder groups including patients, researchers, private industry, journals professional...
2527 Background: AU-007 is a computationally designed human mAb that binds interleukin-2 (IL-2) on its CD25 binding epitope. bound IL-2 cannot bind trimeric (CD25, CD122, CD132) receptors (IL-2R) regulatory T cells (Tregs), vascular endothelium, or eosinophils, but IL-2’s to dimeric IL-2R (CD122, effector (T eff) and NK unhindered. thus redirects towards eff cell activation, while diminishing Treg activation leak. uniquely generated from expansion, converting Treg-mediated autoinhibitory...
Pharmacodynamic assays are important in clinical trial design to investigate the relationship between drug concentration (pharmacokinetics) and "effect' or biological activity. Increasingly flow cytometry is being used examine pharmacodynamic effect of new entities. However, date, analytical validation based limited there no suitable guidance for method cytometry-based assays. Here we report a chemokine internalization assay use evaluating receptor antagonist trials. The was validated by...
Abstract The clinical success of antibody-mediated immune checkpoint blockade therapies has transformed the cancer therapy paradigm by demonstrating that durable antitumor responses and long-term remissions may be achieved in a subset patients across diverse range cancers. However, majority fail to respond antibody targeting single pathways antibodies exhibit long vivo half-life (&gt;15-20 days with &gt;70% target occupancy for months) which contribute emergence immune-related...
Stimulating effector T-cells (Teffs) without inducing regulatory (Tregs) has been the primary goal of IL-2-based therapies for cancer. Recently, modified IL-2 designed differential T-cell expansion treatment cancer failed in clinic. We propose that treatments based on exogenous administrations are inherently undermined by a negative feedback loop, caused secreted endogenously from activated T-cells. This endogenous secretion subsequentially induces Treg and inhibits immune response is...