Volume 3.17 | May 13

Immune Regulation News 3.17, May 13, 2011
     In this issue: Science News | Current Publications | Industry News | Policy News | Events
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TOP STORY

Tumors Use White Blood Cells to Halt Treatment in its Tracks
Scientists have discovered that tumors are able to recruit part of the body’s defense system to protect them from the effect of a drug designed to block the supply of blood to the tumor. [Press release from Cancer Research UK discussing online prepublication in The Journal of Clinical Investigation]

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SCIENCE NEWS

Scientists Use Genetically Altered Virus to Get Tumors to Tattle on Themselves
Scientists have used a genetically re-engineered herpes virus that selectively hunts down and infects cancerous tumors and then delivers genetic material that prompts cancers to secrete a biomarker and reveal their presence. [Press release from the Cincinnati Children’s Hospital Medical Center discussing online prepublication in PLoS ONE]

Scripps Research Scientists Show How Shifts in Temperature Prime Immune Response
Researchers have found a temperature-sensing protein within immune cells that, when tripped, allows calcium to pour in and activate an immune response. [Press release from The Scripps Research Institute discussing online prepublication Nature Chemical Biology]

Immune System Malfunction May Trigger Inflammatory Bowel Disease
Researchers have identified a previously unknown sensor regulating the composition of certain intestinal bacterial microflora. They also found the absence of this regulating sensor results in a dramatic alteration of the microbial environment of the intestines – increasing the risk of developing inflammatory bowel disease. [Press release from Yale University discussing online prepublication in Cell]

Important Step in Breakdown of HIV Proteins is Critical to Immune System Recognition, Destruction of Infected Cells
Researchers have found that – as HIV proteins are broken down within cells, a process that should lead to labeling infected cell for destruction by CD8 T cells – there is a great variability in the stability of resulting protein segments, variations that could significantly change how well cells are recognized by the immune system. [Press release from the Ragon Institute of MGH, MIT and Harvard discussing online prepublication in The Journal of Clinical Investigation]

Inovio Pharmaceuticals Reports Long-Term Immune Responses from Therapeutic Cervical Dysplasia and Cancer DNA Vaccine
Strong, persistent T cell responses in 91% of assessed patients in the Phase I study further validate vaccine’s potential utility in current Phase II study. [Press release from Inovio Pharmaceuticals discussing data presented at the 15th Annual Conference on Women’s Health Care Issues]

Non-Human Primate Studies Reveal Promising Vaccine Approach for HIV
Research conducted has developed a vaccine candidate in non-human primates that may eventually lead to a vaccine against Human Immunodeficiency Virus (HIV). [Press release from Oregon Health & Science University discussing online prepublication in Nature]

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CURRENT PUBLICATIONS (Ranked by Impact Factor of the Journal)

Profound Early Control of Highly Pathogenic SIV by an Effector Memory T-Cell Vaccine
Scientists report that simian immunodeficiency virus (SIV) vaccines that include rhesus cytomegalovirus vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIVMAC239 infection early after mucosal challenge. [Nature]

NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
Here, researchers show that deficiency of NLRP6 in mouse colonic epithelial cells results in reduced IL-18 levels and altered fecal microbiota characterized by expanded representation of the bacterial phyla Bacteroidetes (Prevotellaceae) and TM7. [Cell]

Genetic Analysis of Basophil Function In Vivo
Using sensitive interleukin 4 (Il4) reporter alleles, researchers demonstrate here that basophil IL-4 production occurs by a CD4+ T cell–dependent process restricted to the peripheral tissues affected. [Nat Immunol]

The Nod2 Sensor Promotes Intestinal Pathogen Eradication via the Chemokine CCL2-Dependent Recruitment of Inflammatory Monocytes
Researchers found that Nod2-/- mice exhibited impaired intestinal clearance of Citrobacter rodentium, an enteric bacterium that models human infection by pathogenic Escherichia coli. [Immunity]

The Myeloid Transcription Factor KLF2 Regulates the Host Response to Polymicrobial Infection and Endotoxic Shock
Herein, researchers identify the Kruppel-like transcription factor 2 (KLF2) as a potent regulator of myeloid cell activation in vivo. [Immunity]

Temperature-Dependent STIM1 Activation Induces Ca2+ Influx and Modulates Gene Expression
Ca2+ entry into many cell types including immune cells is triggered by depleting endoplasmic reticulum (ER) Ca2+, a process termed store-operated Ca2+ entry (SOCE). STIM1 is an ER Ca2+ sensor. Upon Ca2+ store depletion, STIM1 clusters at ER–plasma membrane junctions where it interacts with and gates Ca2+-permeable Orai1 ion channels. Here researchers show that STIM1 is also activated by temperature. [Nat Chem Biol]

TIE2-Expressing Macrophages Limit the Therapeutic Efficacy of the Vascular-Disrupting Agent Combretastatin A4 Phosphate in Mice
Scientists show that combretastatin A4 phosphate-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages . [J Clin Invest]

Variable HIV Peptide Stability in Human Cytosol is Critical to Epitope Presentation and Immune Escape
Here, researchers have demonstrated that the half-lives of HIV-derived peptides in cytosol from primary human cells were highly variable and sequence dependent, and significantly affected the efficiency of cell recognition by CD8+ T cells. [J Clin Invest]

Human Bone Marrow Hosts Polyfunctional Memory CD4+ and CD8+ T Cells with Close Contact to IL-15–Producing Cells
In this study, researchers demonstrate that CD4+ and CD8+ effector memory T cells accumulate in the human bone marrow and are in a heightened activation state as revealed by CD69 expression. [J Immunol]

Inhibiting CXCR3-Dependent CD8+ T Cell Trafficking Enhances Tolerance Induction in a Mouse Model of Lung Rejection
Researchers demonstrate in an adoptive transfer model of lung rejection that CXCR3-deficient CD8+ effector T lymphocytes (Teff) have impaired migration into the lungs compared with wild-type Teff, which results in a dramatic reduction in fatal pulmonary inflammation. [J Immunol]

Cancer Screening by Systemic Administration of a Gene Delivery Vector Encoding Tumor-Selective Secretable Biomarker Expression
Researchers exploited tumor-selective replication of a conditionally replicative Herpes simplex virus (HSV) combined with a replication-dependent late viral promoter to achieve tumor-selective biomarker expression as an example gene delivery vector. [PLoS ONE]

INDUSTRY NEWS

University and Pharmaceutical Industry Create Centre for Inflammation Research
The University of Manchester, GlaxoSmithKline and AstraZeneca announce the creation of the Manchester Collaborative Centre for Inflammation Research, a unique collaboration to establish a world-leading translational centre for inflammatory diseases. The project starts out with an initial investment of £5M from each partner over a three year period. [The University of Manchester Press Release]

Pfizer’s Prevnar 13® Meets All Study Endpoints In Two Pivotal Phase 3 Trials In Adults Aged 50 And Older
Pfizer Inc. announced that the data from its two pivotal Phase 3 immunogenicity and safety trials of Prevnar 13®* (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) in adults aged 50 years and older met all study endpoints. [Pfizer Inc. Press Release]

Inovio Pharmaceuticals’ Market-Leading Intellectual Property Recognized by MDB Capital Award
Inovio Pharmaceuticals, Inc., a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced that MDB Capital Group has recognized Inovio with its CLARUS Award, given annually to publicly traded companies possessing market-changing intellectually property assets. [Inovio Pharmaceuticals, Inc.]

POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)

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)

EVENTS

NEW 2nd International Conference on Immune Tolerance
October 23-25, 2011
Amsterdam, The Netherlands

Visit our events page to see a complete list of events in the immune regulation community.

JOB OPPORTUNITIES

Scientist – Human Monoclonal Antibody Discovery (Arsanis Biosciences)

Implementation Coordinator – Maternity Leave Contract (STEMSOFT Software Inc.)

Postdoctoral Research Position – Mucosal Immunology (Department of Microbiology and Immunology, Columbia University)

Research Officer Antibody Engineering (Glenmark Pharmaceuticals S.A.)


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