A5012103124- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune cells in cancer
- Melanoma and MAPK Pathways
- Cancer Mechanisms and Therapy
- Psoriasis: Treatment and Pathogenesis
- IL-33, ST2, and ILC Pathways
- Plant-derived Lignans Synthesis and Bioactivity
- Bioactive Compounds and Antitumor Agents
- Bioactive natural compounds
- Ferroptosis and cancer prognosis
- Pharmacology and Obesity Treatment
- Peroxisome Proliferator-Activated Receptors
- Inflammatory Bowel Disease
- Monoclonal and Polyclonal Antibodies Research
- Whipple's Disease and Interleukins
- Cytokine Signaling Pathways and Interactions
- Natural Antidiabetic Agents Studies
- Colorectal Cancer Treatments and Studies
- Asthma and respiratory diseases
- T-cell and B-cell Immunology
- Protein Tyrosine Phosphatases
- Eosinophilic Esophagitis
Genentech
2013
Genetic Information Research Institute
2002
Uncontrolled mucosal immunity in the gastrointestinal tract of humans results chronic inflammatory bowel disease (IBD), such as Crohn and ulcerative colitis. In early clinical trials well animal models, IL-12 has been implicated a major mediator these diseases based on ability anti-p40 mAb treatment to reverse intestinal inflammation. The cytokine IL-23 shares same p40 subunit with IL-12, mAbs used human mouse IBD studies neutralized activities both IL-23. IL-10-deficient mice spontaneously...
Programmed cell death-1 (PD-1) is a coinhibitory receptor that suppresses T activation and an important cancer immunotherapy target. Upon by its ligand PD-L1, PD-1 thought to suppress signaling through the (TCR). By titrating in biochemical reconstitution system, we demonstrate co-receptor CD28 strongly preferred over TCR as target for dephosphorylation PD-1-recruited Shp2 phosphatase. We also show CD28, but not TCR, preferentially dephosphorylated response PD-L1 intact system. These results...
IL-23 is a heterodimeric cytokine composed of the IL-12p40 "soluble receptor" subunit and novel cytokine-like related to IL-12p35, termed p19. Human mouse exhibit some activities similar IL-12, but differ in their capacities stimulate particular populations memory T cells. Like binds IL-12R IL-12Rbeta1. However, it does not use IL-12Rbeta2. In this study, we identify member hemopoietin receptor family as for IL-23, "IL-23R." IL-23R pairs with IL-12Rbeta1 confer responsiveness on cells...
PD-1 (programmed cell death-1) is the central inhibitory receptor regulating CD8 T exhaustion during chronic viral infection and cancer. Interestingly, also expressed transiently by activated cells acute infection, but role of in modulating effector differentiation function not well defined. To address this question, we examined expression kinetics lymphocytic choriomeningitis virus (LCMV) mice. was rapidly up-regulated vivo upon activation naive virus-specific within 24 h after LCMV less...
Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication immune system. Therapeutic use blocking antibodies to PD-L1 or its PD-1 has produced unparalleled, durable clinical responses, with highest likelihood response seen in patients whose tumour cells express before therapy. The significance expression each cell type emerged as a central and controversial unknown development immunotherapeutics. Using...
Abstract Programmed death-1 (PD-1) is a co-inhibitory receptor that suppresses T cell activation and an important cancer immunotherapy target. Upon by its ligand PD-L1, PD-1 thought to suppress signaling through the (TCR). Here, titrating strength of in both biochemical reconstitution systems cells, we demonstrate coreceptor CD28 strongly preferred over TCR as target for dephosphorylation PD-1- recruited Shp2 phosphatase. We also show colocalizes with costimulatory plasma membrane...
Abstract Immunotherapy with checkpoint inhibitors has proved to be highly effective, durable responses in a subset of patients. Given their encouraging clinical activity, are increasingly being tested trials combination chemotherapy. In many instances, there is little understanding how chemotherapy might influence the quality immune response generated by inhibitors. this study, we evaluated impact alone or anti–PD-L1 responsive syngeneic tumor model. Although multiple classes treatment...
Background Cancer immunotherapy has evolved from interferon-alpha (IFNα) and interleukin-2 in the 1980s to CTLA-4 PD-1/PD-L1 checkpoint inhibitors (CPIs), latter highlighting importance of enhancing T-cell functions. While search for novel immunomodulatory pathways continues, combination therapies augmenting multiple can also increase efficacy. The association autoimmune-related adverse events with clinical efficacy following CPI treatment been inferred suggests that breaking tolerance...
Using an ethnomedical-based drug discovery program, two previously unknown compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 SP-18905 are terpenoid-type quinones significantly lowered plasma concentration (p <.05) when given orally to either ob/ob or db/db mice, both which hyperglycemic hyperinsulinemic. The antihyperglycemic actions associated with significant decreases insulin <.05),...
Meeting abstracts Pharmacological inhibition of the MAPK pathway with MEK or BRAF antagonists has proved successful in inducing regression melanoma tumors bearing targeted activating mutations. Moreover, antibodies targeting T-cell immune checkpoint inhibitors CTLA-4 PD-L1/PD-1 have
Abstract CD4 T cells have long been known to be critical for priming CD8 cells, a process referred as cell help. Recent data suggested that help may delivered at the surface of conventional type 1 dendritic (cDC1s), which can efficiently present antigens (Ag) on both MHC class I and II molecules. However, actual mechanisms underlying remain poorly characterized. We sought understand how anti-tumor responses are generated in context mRNA vaccines, shown elicit protective and/or cells. For...
Abstract Immunotherapeutic agents have shown dramatic success in oncology recent years and several been approved melanoma lung cancer. One strategy for extending the benefit of immunotherapy is to evaluate these combination with standard care chemotherapy, goal bringing into earlier lines treatment. We carried out a systematic evaluation effects different classes chemotherapeutic (including alkylating agents, platinum based taxanes) on tumor immune microenvironment syngeneic murine models...
Abstract Immunotherapeutic agents have shown great promise in the clinic recent years and this has led to their approval as single or immune doublet combinations melanoma lung cancer. In order increase extent of benefit from these extend immunotherapies additional patients, are being evaluated immunotherapeutic with chemotherapy targeted agents. Inhibitors mitogen-activated kinase protein (MAPK) pathway, including BRAF MEK inhibitors, been approved melanoma, indications. We effects ERK...
Abstract Immunotherapy with checkpoint inhibitors has proven to be highly effective, durable responses in a subset of patients. In an effort broaden the number responding individuals, overcome resistance single-agent therapy and extend duration responses, combination immunotherapy other treatments such as chemotherapy is currently being tested multiple clinical trials. Importantly, standard care could bring benefits into earlier lines treatment. Here, we have evaluated effects different...
<h3>Background</h3> The development of adoptive cell therapy has made the understanding T-cell target recognition and activation crucial to cancer treatment. Indeed, success many these therapies directly depends on our ability predict or measure specificity receptors (TCR) neoantigens understand how specificities translate into activation. While dynamics TCR-pMHC binding have been under careful scrutiny for a long time, fundamental unknowns remain regarding aspects that relate immune...