Immune Regulation News Volume 6.17 | May 16 2014

Tolerance Induction in Memory CD4 T Cells Requires Two Rounds of Antigen-Specific Activation
Researchers used MHC class II tetramers to track and analyze a population of endogenous antigen-specific memory CD4 T cells exposed to soluble peptide in the absence of adjuvant. They found that such memory T cells proliferated and reentered the memory pool apparently unperturbed by the incomplete activation signals provided by the peptide. [Proc Natl Acad Sci USA] Abstract

T Cell Receptor Signals to Nuclear Factor κB Are Transmitted by a Cytosolic p62-Bcl10-Malt1-IKK Signalosome
Scientists found that the active inhibitor of κB kinase (IKK) complex is a component of a T cell receptor-dependent cytosolic Bcl10-Malt1 signalosome containing the adaptor protein p62, which forms in effector T cells. [Sci Signal] Abstract | Press Release

Protein Tyrosine Phosphatase 1B Is a Regulator of the Interleukin-10-Induced Transcriptional Program in Macrophages
Researchers examined the role of protein tyrosine phosphatase 1B (PTP1B) in regulating the interleukin (IL)-10-dependent, signal transducer and activator of transcription 3 (STAT3)-mediated anti-inflammatory response. They found that IL-10-dependent STAT3 phosphorylation and anti-inflammatory gene expression were enhanced in macrophages from PTP1B^-/- mice compared to those in macrophages from wild-type mice. [Sci Signal] Abstract

Effector-Mediated Eradication of Precursor B Acute Lymphoblastic Leukemia with a Novel Fc-Engineered Monoclonal Antibody Targeting the BAFF-R
Researchers tested a novel humanized anti-BAFF-R (B-cell activating factor receptor) monoclonal antibody optimalized for FcRγIII-mediated, antibody-dependent cell killing by effector cells. The antibodies significantly stimulated natural killer cell-mediated killing of different human patient-derived acute lymphoblastic leukemia cells. [Mol Cancer Ther] Abstract | Press Release

Essential Role of Elmo1 in Dock2-Dependent Lymphocyte Migration
Researchers showed that endogenous Elmo1, but not Elmo2, interacts constitutively with Dock2 in mouse and human primary T cells. CD4⁺ T cells from Elmo1^−/− mice were profoundly impaired in polarization, Rac activation, and chemotaxis in response to CCR7 and CXCR4 stimulation. [J Immunol] Abstract

Caerulomycin A Enhances the TGF-β-Smad3 Signaling by Suppressing IFN-γ-STAT1 Signaling to Expand Tregs
Scientists report a novel role of a bipyridyl compound Caerulomycin A (CaeA) in inducing the generation of regulatory T cells (Tregs). It was observed that CaeA substantially upregulated the pool of Tregs, as evidenced by increased frequency of CD4⁺ Foxp3⁺ cells. In addition, CaeA significantly suppressed the number of T helper type (Th)1 and Th17 cells, as supported by decreased percentage of CD4⁺/IFN-γ⁺ and CD4⁺/interleukin-17⁺ cells, respectively. [J Biol Chem] Abstract | Full Article

Inhibition of B7-1 (CD80) by RhuDex^® Reduces Lipopolysaccharide-Mediated Inflammation in Human Atherosclerotic Lesions
Carotid artery plaque stimulation with lipopolysaccharides could be significantly inhibited by RhuDex^®, a specific inhibitor of the costimulatory molecule B7-1 ex vivo. Coculture of antigen-presenting cells with T-cells demonstrated that the inhibitory effects of RhuDex^® derived from reduced T-cell activation. [Drug Des Devel Ther] Abstract

Ovarian Tumor-Associated MicroRNA-20a Decreases Natural Killer Cell Cytotoxicity by Downregulating MICA/B Expression
Reduction of membrane-bound MICA/B proteins, which are ligands of the natural killer group 2 member D (NKG2D) receptor found on natural killer cells, γδ⁺ T cells and CD8⁺ T cells, allowed tumor cells to evade immune-mediated killing. Notably, antagonizing miR-20a action enhanced the NKG2D-mediated killing of tumor cells in both in vitro and in vivo models of tumors. [Cell Mol Immunol] Abstract

The Pleiotropic Functions of TNF-α in the Regulation of the Intestinal Epithelial Response to Inflammation
Tumor necrosis factor (TNF-α) impacts epithelial wound healing in ErbB- and Wnt-dependent pathways while also importantly guiding immune cell attraction and function. The authors focus on functional in vivo data providing crucial insights into the complex process of intestinal homeostasis. [Int Immunol]
Abstract | Full Article

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NewLink Genetics to Present at the ASCO 2014 Annual Meeting
NewLink Genetics Corporation announced presentations highlighting its HyperAcute^® and IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor programs. [Press release from NewLink Genetics Corporation discussing research to be presented at the 50^th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

Sequenta and Collaborators to Present Lymphoma and Immunotherapy Data
Sequenta, Inc. and its academic collaborators will share data gathered with the company’s immune repertoire profiling technology, the LymphoSIGHT™ platform, in two presentations. [Press release from Sequenta, Inc. discussing research to be presented at the 50^th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

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NeoStem Announces Licensing Agreement and Plans to Begin Phase II Hepatocellular Carcinoma Trial in China
NeoStem, Inc. has signed an exclusive license agreement with China-based Cellular Biomedicine Group to begin a Phase II clinical trial in patients with late stage liver cancer. The trial, to be conducted in China in accordance with international standards, will investigate the use of the company’s developmental patient-specific cancer immunotherapy known as “DC-TC,” in patients with hepatocellular carcinoma. [NeoStem, Inc.] Press Release

Telik and MabVax Therapeutics Announce Definitive Merger Agreement
Telik, Inc. and MabVax Therapeutics, Inc. have entered into a definitive merger agreement. Upon closing of the transaction, MabVax and Telik will be combined into a publicly traded company focused on the development of proprietary immunotherapy-based products to diagnose and treat cancer. [PR Newswire Association LLC] Press Release

Amgen and AstraZeneca Announce Positive Results from Phase III Study of Brodalumab (AMG 827) in Patients with Moderate-to-Severe Plaque Psoriasis
Amgen and AstraZeneca announced that the Phase III AMAGINE-1™ study evaluating brodalumab in patients with moderate-to-severe plaque psoriasis met all primary and secondary endpoints for both evaluated doses. Brodalumab is the only investigational treatment in development that binds to the interleukin-17 (IL-17) receptor and inhibits inflammatory signaling by blocking the binding of several IL-17 ligands to the receptor. [Amgen Inc.] Press Release

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Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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NEW Postdoctoral Position – Cell Death and Inflammation (Inflammation Research Center – VIB-UGent)

NEW Postdoctoral Position – Cell and Extracellular Matrix Biology (Johns Hopkins University)

Principal Investigator – Molecular Mechanisms of Inflammation (Inflammation Research Center – VIB-UGent)

Postdoctoral Fellow – Microbiology and Immunology (McGill University)

Postdoctoral Research Associate – Functional Cross-Talk between T Lymphocytes and NK Cells (Meharry Medical College School of Medicine)

Postdoctoral Associate/Research Scientist – Macrophage Biology (Massachusetts Institute of Technology – MIT)

Postdoctoral Associate – Immunology (Virginia Bioinformatics Institute at Virginia Tech)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

PhD Research Position – Molecular and Cellular Mechanisms of Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – hPSC (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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