A5103176869- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Bladder and Urothelial Cancer Treatments
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Cancer Immunotherapy and Biomarkers
- Urinary and Genital Oncology Studies
- Industrial Technology and Control Systems
- Adolescent Sexual and Reproductive Health
- Water Quality Monitoring and Analysis
- Fault Detection and Control Systems
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- HIV, Drug Use, Sexual Risk
- Genetic Associations and Epidemiology
- interferon and immune responses
- Statistical Methods in Clinical Trials
- Aquaculture disease management and microbiota
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Hepatitis C virus research
- Invertebrate Immune Response Mechanisms
- TGF-β signaling in diseases
- Developmental Biology and Gene Regulation
Seagen (United States)
2019-2025
Pfizer (United States)
2024-2025
Powerchina Huadong Engineering Corporation (China)
2021
PowerChina (China)
2021
Fred Hutch Cancer Center
2008-2017
Cancer Research And Biostatistics
2010-2015
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2011-2014
Army Medical University
2012-2013
421 Hospital of PLA
2013
Xinqiao Hospital
2013
The characterization of the cross-reactive, or heterologous, neutralizing antibody responses developed during human immunodeficiency virus type 1 (HIV-1) infection and identification factors associated with their generation are relevant to development an HIV vaccine. We report that in healthy HIV-positive, antiretroviral-naïve subjects, breadth plasma heterologous correlates time since infection, viremia levels, binding avidity anti-Env antibodies. Anti-CD4-binding site antibodies...
No treatment has surpassed platinum-based chemotherapy in improving overall survival patients with previously untreated locally advanced or metastatic urothelial carcinoma. Download a PDF of the Research Summary. We conducted phase 3, global, open-label, randomized trial to compare efficacy and safety enfortumab vedotin pembrolizumab Patients were randomly assigned 1:1 ratio receive 3-week cycles (at dose 1.25 mg per kilogram body weight intravenously on days 1 8) 200 day 1) (enfortumab...
664 Background: EV-302 /KEYNOTE-A39 (NCT04223856) demonstrated significant progression-free survival (PFS) and overall (OS) benefit with first-line (1L) EV+P vs chemo in patients (pts) la/mUC. is the standard of care (SOC) global treatment guidelines for pts untreated We present 12 mo additional follow-up (>2 y median follow-up) an exploratory analysis confirmed complete response (cCR). Methods: Pts previously la/mUC were randomized 1:1 to receive EV (1.25 mg/kg; Days 1 8; IV) P (200 mg;...
Background The V3 loop of the HIV-1 envelope (Env) glycoprotein gp120 was identified as “principal neutralizing domain” HIV-1, but has been considered too variable to serve a antibody (Ab) target. Structural and immunochemical data suggest, however, that contains conserved elements which explain its role in binding virus co-receptors despite sequence variability. Despite this evidence conservation, ability anti-V3 Abs neutralize significant proportion isolates from different subtypes...
Background Seroadaptation strategies such as serosorting and seropositioning originated within communities of men who have sex with (MSM), but there are limited data about their effectiveness in preventing HIV transmission when utilized by HIV-negative men. Methodology/Principal Findings Data from the EXPLORE cohort MSM reported both seroconcordant serodiscordant partners were used to evaluate seropositioning. The association seroconversion was evaluated this high risk six U.S. cities....
A successful HIV vaccine will likely induce both humoral and cell-mediated immunity, however, the enormous diversity of has hampered development a that effectively elicits arms adaptive immune response. To tackle problem viral diversity, T cell-based approaches have focused on two main strategies (i) increasing breadth vaccine-induced responses or (ii) targeting only conserved regions virus. The relative extent to which set-point viremia is impacted by epitope-conservation CD8+ cell elicited...
Background Cluster of differentiation 70 (CD70) is frequently expressed in renal cell carcinoma (RCC) and has immunomodulatory properties. An antibody‐drug conjugate targeting CD70, SGN‐CD70A, was developed to treat patients with CD70‐positive RCC. Methods The objective this phase 1, open‐label, dose‐escalation, multicenter study evaluate the safety tolerability SGN‐CD70A establish its maximum tolerated dose CD70‐positive, metastatic RCC (mRCC). All subtypes were permitted, no limit set on...
Abstract Several kindreds of Volga German (VG) ancestry have a single PS2 mutation that causes an autosomal dominant form Alzheimer's disease (AD). These families show wide range in age‐at‐onset, which suggests the existence modifying factors other than mutation. To examine evidence for genetic basis variation onset age, we performed Bayesian oligogenic segregation and linkage analysis on nine VG confirmed to at least one affected carrier. This simultaneously estimated effects APOE number...
Abstract In this study, we used a systems vaccinology approach to identify temporal changes in immune response signatures the yellow fever (YF)-17D vaccine, with aim of comprehensively characterizing responses associated protective immunity. We conducted cohort study which 21 healthy subjects China were administered one dose YF-17D vaccine; PBMCs collected at 0 h and then 4 days 1, 2, 3, 5, 7, 14, 28, 84, 168 postvaccination, analyzed by transcriptional profiling immunological assays. At...
ABSTRACT We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused gp140, were administered as boost poly-ICLC adjuvant alone coadministered NYVAC-KC vector. All vaccine administrations increased low-level serum...
Abstract In seeking evidence of the existence adaptive immune system (AIS) in ancient chordate, cDNA clones six libraries from a protochordate, Chinese amphioxus, were sequenced. Although key molecules such as TCR, MHC, Ig, and RAG AIS have not been identified our database, we demonstrated this study extensive molecular for presence genes homologous to many that are involved directly or indirectly, including some which may represent putative precursors vertebrate AIS-related genes. The...
Neutralizing antibody assays are widely used in research toward the development of a preventive HIV-1 vaccine. Currently, neutralization potency an is typically quantified by inhibitory concentration (IC) values (e.g., IC50), and breadth estimated empirical method. In this article, we propose area under curve (AUC) partial (pAUC) measures for summarizing titration curve, which complement commonly IC measure. We present multiple advantages AUC over IC50, include no complications due to...
Non-linear calibration is a widely used method for quantifying biomarkers wherein concentration-response curves estimated using samples of known concentrations are to predict the biomarker in interest. The R package nCal fills an important gap open source, stand-alone software performing non-linear calibration. For curve fitting, provides new implementation robust, Bayesian hierarchical five-parameter logistic model. supports simple graphical user interface that can be by laboratory...
Both the four-parameter logistic (4PL) and five-parameter (5PL) models are widely used in nonlinear calibration. In this paper, we study choice between 5PL 4PL both by accuracy precision of estimated concentrations power to detect an association a binary disease outcome concentrations. Our results show that when true curve is symmetric around its inflection point, efficiency loss from using negligible under prevalent experimental design. When asymmetric, may sometimes offer better...
Background Defining optimal routes for induction of mucosal immunity represents an important research priority the HIV-1 vaccine field. In particular, it remains unclear whether immunization can improve immune responses. Methods this randomized two center phase I clinical trial we evaluated systemic and response to a candidate Clade C CN54gp140 envelope glycoprotein administered by intramuscular (IM), intranasal (IN) intravaginal (IVAG) administration in HIV negative female volunteers. IM...
Background A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity DNA prime co-expressing GM-CSF (Dg) followed by different numbers intervals modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env. Methods Four US sites randomized 48 participants to receiving 1/10th dose as DgDgMMM given at 0, 2, 4, 6 8 months, or full DgDgM_M DgDgMM_M regimens, 6, 10 respectively. Peak was measured 2...
Plain Language SummaryWhat is this summary about?This a of the publication EV-302/KEYNOTE-A39 study that was published in The New England Journal Medicine March 2024. helped researchers learn more about possible new treatment for advanced urothelial cancer. Urothelial cancer starts bladder or other parts urinary tract.Platinum-based chemotherapy usually first therapy used to treat cancer, but platinum-based does not always work and can have many side effects. In study, tested how well drug...
4571 Background: EV-302/KEYNOTE-A39 (NCT04223856) demonstrated superior efficacy of first-line (1L) EV+P vs chemo and established as the standard care (SOC). is included in global treatment guidelines for patients (pts) with untreated la/mUC. After ≈2.5 years median follow-up, benefit was sustained; OS maintained > 2.5 years. We present long-term safety analyses following prespecified subgroups: primary disease site origin (upper lower tracts), lymph node (LN)–only disease, presence liver...
4502 Background: EV-302/KEYNOTE-A39 (NCT04223856) showed significant PFS and OS benefits for pts with previously untreated la/mUC treated EV+P vs chemo, which established as the SOC in this population. This exploratory analysis presents efficacy safety results responders, focusing on confirmed complete response (cCR). Methods: Pts were randomized 1:1 to receive EV (1.25 mg/kg; Days 1 8; IV) + P (200 mg; Day 1; or chemo (gemcitabine cisplatin/carboplatin); all Q3W. Primary endpoints by BICR...