A5063609469- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Geriatric Care and Nursing Homes
- Immune Response and Inflammation
- Radiopharmaceutical Chemistry and Applications
- Atherosclerosis and Cardiovascular Diseases
- Prostate Cancer Treatment and Research
- Frailty in Older Adults
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- Systemic Lupus Erythematosus Research
- interferon and immune responses
- Glycosylation and Glycoproteins Research
- vaccines and immunoinformatics approaches
- Synthesis and Biological Evaluation
- Climate Change and Health Impacts
- SARS-CoV-2 and COVID-19 Research
- Healthcare Policy and Management
- Cancer Research and Treatments
- Psoriasis: Treatment and Pathogenesis
Providence Portland Medical Center
2015-2024
Cancer Institute (WIA)
2022
Fraunhofer Chile Research Foundation
2022
Cancer Research Center
2008-2019
Leiden University Medical Center
2019
St. Joseph Health System
2019
Providence College
2019
Oregon Health & Science University
1997-2015
Vaccine and Gene Therapy Institute
2013
Providence Regional Medical Center Everett
2006-2013
Our studies show that the presence of IL-4 during response naive Th cells causes precursors to develop into a population comprised largely "Th2-like" effectors secrete and IL-5, but little IL-2 or IFN-gamma. We find levels determine both level developed in mitogen Ag patterns lymphokines they when restimulated. is required for optimum generation effectors, increasing IL-2, augments expansion secreting IL-4/IL-5 In contrast, development suppresses at higher doses IFN-gamma-secreting detected...
Abstract Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103 + CD39 tumor-infiltrating CD8 (CD8 TIL) are enriched tumor-reactive both in primary metastatic tumors. This TIL subset is found across six different malignancies displays an exhausted tissue-resident memory phenotype. TILs have a distinct T-cell receptor (TCR) repertoire, with clones expanded the but present at low...
Ox-40 and ligand (Ox-40L) are thought to be involved in T cell-APC interactions. However, their exact role cell responses is undefined. Using fibroblast transfectants expressing Ox-40L and/or B7-1, CD4 cells from TCR transgenic mice, we investigated the effect of signaling on primary Ag pigeon cytochrome c. expression naive peaked 2 3 days after activation, was lost by 4 5 days. APCs with promoted partial activation some IL-2 secretion, but were unable enhance proliferation, unlike those...
Abstract OX40 is a potent costimulatory receptor that can potentiate T-cell signaling on the surface of T lymphocytes, leading to their activation by specifically recognized antigen. In particular, engagement ligands present dendritic cells dramatically increases proliferation, effector function, and survival cells. Preclinical studies have shown agonists increase antitumor immunity improve tumor-free survival. this study, we performed phase I clinical trial using mouse monoclonal antibody...
Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity tumor-bearing hosts. Here we describe results from a phase Ib clinical trial (NCT02274155) which 17 patients with locally advanced head neck squamous carcinoma (HNSCC) received murine anti-human OX40 agonist antibody (MEDI6469) prior definitive surgical...
Abstract The costimulatory receptor OX40 has recently been shown to be involved in primary CD4 responses several defined Ags. However, date there little information regarding the mechanism of action OX40, such as whether it regulates T cell numbers, reactivity, or both, and contributes induction long-term responses. With an agonist Ab by tracking Ag-specific TCR transgenic cells vivo, we show that ligation induces clonal expansion survival during responses, results accumulation greater...
Abstract The OX-40 receptor (OX-40R), a member of the TNFR family, is primarily expressed on activated CD4+ T lymphocytes. Engagement OX-40R, with either ligand (OX-40L) or an Ab agonist, delivers strong costimulatory signal to effector cells. OX-40R+ cells isolated from inflammatory lesions in CNS animals experimental autoimmune encephalomyelitis are that respond autoantigen (myelin basic protein) vivo. We identified within primary tumors and tumor-invaded lymph nodes patients cancer...
We have investigated the effects of TGF-beta on in vitro development different subsets Th cells and find that addition results generation cell populations with distinct characteristics resemble those memory cells. Resting, short-lived CD4+ precursor T can be induced by mitogen stimulation to proliferate differentiate cultures after 4 7 days will generate a population that, when restimulated, synthesize secrete high titers wide variety lymphokines. It has been previously reported presence...
Abstract The OX-40R is a member of the TNF receptor family and expressed primarily on activated CD4+ T cells. When engaged by OX-40 ligand (OX-40L), potent costimulatory signal occurs. We have identified population CD11b+ cells, isolated from central nervous system (CNS) mice with actively induced experimental allergic encephalomyelitis (EAE), that expresses OX-40L. Moreover, expression OX-40L was found to be associated paralytic episodes EAE reduced or absent at disease recovery. These...
Abstract This report defines a cell surface receptor (OX40) expressed on effector CD4 T cells, which when engaged in conjunction with danger signal, rescues Ag-stimulated cells from activation-induced death vivo. Specifically, three signals were necessary to promote optimal generation of long-lived memory vivo: Ag, signal (LPS), and OX40 engagement. Mice treated Ag or superantigen (SAg) alone produced very few SAg-specific cells. ligation LPS stimulation, enhanced SAg-driven clonal expansion...
Expansion and recruitment of CD4(+) Foxp3(+) regulatory T (T reg) cells are mechanisms used by growing tumors to evade immune elimination. In addition expansion effector cells, successful therapeutic interventions may require reduction reg within the tumor microenvironment. We report that combined use alkylating agent cyclophosphamide (CTX) an agonist antibody targeting co-stimulatory receptor OX40 (OX86) provides potent antitumor immunity capable regressing established, poorly immunogenic...
<h3>Objective.</h3> —To review published literature regarding dehydration in older individuals and formulate a consensus on the evaluation treatment of this unrecognized cause hospitalizations, morbidity, mortality. <h3>Data Sources Study Selection.</h3> —The concerning elderly population from MEDLINE was reviewed 1976 through 1995. Search terms included<i>dehydration, elderly, evaluation, hospitalization</i>, and<i>treatment</i>. Particular emphasis placed articles describing original...
Abstract We have shown that the requirements for production of IL-4 and IL-5 by normal L3T4+T cells from murine spleen are very different those IL-2. Secretion detectable quantities induction mRNA each lymphokine occurs in vitro only after primed re-stimulated. This priming can be achieved mitogens (Con A), antibodies to TCR (anti-T3) or stimulation with alloantigen. In contrast, resemble initial Thus majority T helper phenotype potential become IL-4- IL-5-secreting cells, exist form...
Abstract Acquisition of full T-cell effector function and memory differentiation requires appropriate costimulatory signals, including ligation the molecule OX40 (TNFRSF4, CD134). Tumors often grow despite presence tumor-specific T cells establish an environment with weak costimulation immune suppression. Administration agonists has been shown to significantly increase survival tumor-bearing mice was dependent on both CD4 CD8 during priming. To understand how work in established tumors, we...
We report that OX40 stimulation drives all lineages of CD4 T cell development, including regulatory cells (Tregs), and the plasticity response is dependant on local cytokines. In TGF-beta1-treated cultures, an agonist increased IFN-gamma IL-4 production diverted from Treg lineage. However, cytokine blockade in context promoted enhanced accumulation. This observation was evident naive mice, as engagement proliferation accumulation vivo. Lastly, administration influenced experimental...
The tumor recurrence from residual local or micrometastatic disease remains a problem in cancer therapy. In patients with soft tissue sarcoma and the inoperable nonsmall cell lung cancer, is common significant mortality caused by subsequent emergence of metastatic disease. Thus, although aim primary therapy curative, outcome may be improved additional targeting microscopic We display murine model that surgical removal large results approximately 50% animals. Depletion CD8 T cells 100%...