Volume 2.21 | Jun 3

Human Immunology News 2.21 June 3, 2014
Human Immunology News
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Improved Survival with T Cell Clonotype Stability after Anti-CTLA-4 Treatment in Cancer Patients
To determine the effects of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blockade on the T cell repertoire, investigators used next-generation deep sequencing to measure the frequency of individual rearranged T cell receptor β genes, thereby characterizing the diversity of rearrangements, known as T cell clonotypes. [Sci Transl Med] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
CD4 T Cells with Effector Memory Phenotype and Function Develop in the Sterile Environment of the Fetus
Scientists have identified and characterized a population of fetally developed CD4 T cells with an effector memory phenotype, which are present in cord blood. This population is polyclonal and has phenotypic features similar to those of conventional adult memory T cells, such as CD45RO expression. [Sci Transl Med] Abstract

Combinatorial Flexibility of Cytokine Function during Human T Helper Cell Differentiation
Researchers showed that a single cytokine, interferon-alpha, can generate multiple transcriptional signatures, including distinct functional modules of variable flexibility, when acting in four cytokine environments driving distinct T helper cell differentiation programs (Th0, Th1, Th2 and Th17). [Nat Commun] Abstract

Breast Cancer Metastasis: Demonstration That FOXP3 Regulates CXCR4 Expression and the Response to CXCL12
During activation, human T cells show reciprocal regulation of FOXP3 and CXCR4. Researchers examined the role FOXP3 plays in metastatic breast cancer, with a particular focus on its potential to regulate CXCR4. [J Pathol] Abstract

Podocytes Regulate Neutrophil Recruitment by Glomerular Endothelial Cells via IL-6-Mediated Crosstalk
Researchers hypothesized that podocytes influence the ability of glomerular endothelial cells to recruit neutrophils during inflammation. [J Immunol] Abstract

Immunosuppression through Constitutively Activated NF-κB Signaling in Human Ovarian Cancer and Its Reversal by an NF-κB Inhibitor
NF-κB is involved in the immunosuppression induced by human epithelial ovarian cancer (EOC), and its inhibitor may restore antitumor immune responses, indicating that NF-κB is an attractive target for EOC treatment. [Br J Cancer] Abstract

Effects of Low-Dose Recombinant Interleukin 2 to Promote T-Regulatory Cells in Alopecia Areata
An impaired inhibitory function of circulating CD4+CD25+ regulatory T (Treg) cells was reported to play a key role in alopecia areata (AA). Investigators report the first use to their knowledge of low-dose interleukin 2 for treating severe AA by promoting the recruitment of Treg cells. [JAMA Dermatol] Abstract

Phosphorylation of Rab5a by Protein Kinase Cε Is Crucial for T-Cell Migration
Researchers present a novel mechanism by which a protein kinase Cε-Rab5a-Rac1 axis regulates cytoskeleton remodeling and T-cell migration, both of which are central for the adaptive immune response. [J Biol Chem] Abstract | Full Article

An Efficient siRNA-Mediated Gene Silencing in Primary Human Monocytes, Dendritic Cells and Macrophages
Researchers describe a protocol optimized for the lipid-based delivery of siRNA to perform gene silencing in primary human blood monocytes, which is applicable to dendritic cells, and differs from the classical route of siRNA delivery into macrophages. [Immunol Cell Biol] Abstract

Synergistic Effects of IL-4 and TNFalpha on the Induction of B7-H1 in Renal Cell Carcinoma Cells Inhibiting Allogeneic T Cell Proliferation
Cytokine pretreated tumor cells were co-cultured with allogeneic CD8+ T cells from healthy donors and T cell proliferation as well as cytokine secretion was determined. [J Transl Med] Abstract | Full Article

Effect of Everolimus on the Immunomodulation of the Human Neutrophil Inflammatory Response and Activation
Scientists investigated the impact of different immunosuppressive drugs on the inflammatory response of neutrophils isolated from the blood of healthy volunteers. [Cell Mol Immunol] Abstract

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Pattern Recognition Receptors and the Inflammasome in Kidney Disease
Evidence suggests that toll-like receptors, nucleotide-binding oligomerization domain receptors and the NACHT, LRR and PYD domains-containing protein 3 inflammasome have important roles in kidney diseases through regulation of inflammatory and tissue-repair responses to infection and injury. [Nat Rev Nephrol] Abstract

Immunoregulatory Activity of Adenosine and Its Role in Human Cancer Progression
Adenosine signaling downregulates functions of most immune effector cells but enhances expansion and activity of immune cells responsible for suppression of anti-tumor immune responses. [Expert Rev Clin Immunol] Abstract

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New Therapies Harness Power of the Immune System Against Cancer
New research on innovative immunotherapies for advanced or high-risk melanoma and cervical cancer were presented. These treatments – used alone or in combination – fight cancer by activating and amplifying the body’s immune response to the disease. [Press release from the American Society of Clinical Oncology (ASCO) discussing research presented at the 50th Annual Meeting of the ASCO, Chicago] Press Release

ImmunoCellular Therapeutics Presents Updated ICT-107 Phase II Data in Patients with Newly Diagnosed Glioblastoma
ImmunoCellular Therapeutics, Ltd. announced updated efficacy and safety data from the phase II trial of dendritic cell-based immunotherapeutic vaccine ICT-107 in patients with newly diagnosed glioblastoma multiforme. [Press release from ImmunoCellular Therapeutics, Ltd. discussing research presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

Nektar Presents Positive Preclinical Data for NKTR-214, a Novel Cancer Immunotherapy
Nektar Therapeutics announced positive preclinical data for NKTR-214, a new investigational cancer immunotherapy which selectively activates the IL-2 receptor complex and is being developed as a potential treatment for multiple cancers. [Press release from Nektar Therapeutics discussing research presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release | Poster

Advaxis Presents New Long-Term Survival Data Greater than 24-Months
Advaxis, Inc. presented final results from the Phase II clinical study of its lead immunotherapy product candidate, ADXS-HPV (ADXS11-001), in women with recurrent cervical cancer. [Press release from Adavaxis, Inc. discussing research presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

Investigational Immunotherapy Anti-PDL1 (MPDL3280A) Shrank Tumors in 43 Percent of People with a Specific Type of Metastatic Bladder Cancer in a Genentech Study
Genentech announced results from a Phase I open-label study that showed the investigational cancer immunotherapy MPDL3280A (anti-PDL1) shrank tumors in 43 percent of people previously treated for metastatic urothelial bladder cancer whose tumors were characterized as Programmed Death Ligand-1 positive by a test being developed by Roche. [Press release from Genentech, Inc. discussing research presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

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CEL-SCI Receives Approval to Expand Its Immunotherapy Phase III Head and Neck Cancer Trial into the United Kingdom
CEL-SCI Corporation announced the United Kingdom’s Medicines and Healthcare Products Regulatory Agency has granted regulatory approval to begin the company’s Phase III Head and Neck Cancer clinical trial of its investigational cancer immunotherapy treatment Multikine (Leukocyte Interleukin, Injection) in the United Kingdom. [CEL-SCI Corporation] Press Release

Adaptimmune Enters Strategic Cancer Immunotherapy Collaboration with GlaxoSmithKline to Develop and Commercialize Novel Cell-Based Therapies
Adaptimmune Limited announced that it has entered into a strategic collaboration and licensing agreement with GlaxoSmithKline for the development and commercialization of its lead clinical cancer program. Using its unique T-cell receptor (TCR) engineering technology, Adaptimmune has created TCRs which are deployed to target the cancer testis antigen, NY-ESO-1, and other targets. [Adaptimmune Limited] Press Release

Advaxis Selects inVentiv Health Clinical to Conduct Clinical Trials of Immunotherapy Candidates
inVentiv Health Clinical and Advaxis, Inc. announced that they have entered into a global master services agreement for the clinical development of certain immunotherapy product candidates in Advaxis’s proprietary pipeline. [inVentive Health, Inc.] Press Release

Oncothyreon and Celldex Therapeutics Announce Collaboration for Combination Immunotherapy Clinical Trial of ONT-10 and Varlilumab
Oncothyreon Inc. and Celldex Therapeutics, Inc. announced they have agreed to collaborate on a combined clinical trial of ONT-10 and varlilumab. ONT-10 is a therapeutic vaccine targeting the tumor-associated antigen MUC1. Varlilumab is a fully human monoclonal antibody that targets CD27, a critical molecule in the activation pathway of lymphocytes. [Oncothyreon Inc.] Press Release
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NEW BIO Latin America
September 9-11, 2014
Rio de Janeiro, Brazil

Visit our events page to see a complete list of events in the human immunology community.
NEW Cell Biologists – T Cell-Based Therapies (Adaptimmune)

NEW Postdoctoral Positions – Epigenetics in Autoimmune Diseases (Weill Cornell Medical School/Memorial Sloan Kettering Cancer Center)

Senior Scientist – Immunology (Alector LLC)

Postdoctoral Fellow – Immunology (Charité – Universitätsmedizin Berlin)

Research Associate – Cellular Immunology (Alector LLC)

PhD Candidate – Immune Monitoring (Erasmus MC)

Postdoctoral Scholar – Cancer Research (University of Chicago)

PhD Studentship – Characterization of Human Antibodies Removed from the Repertoire in Central Tolerance (King’s College London)

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

Postdoctoral Fellow – Systemic Autoimmunity (Oklahoma Medical Research Foundation)

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

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – hPSC (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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

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

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