Volume 2.43 | Nov 18

Human Immunology News 2.43 November 18, 2014
Human Immunology News
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TLR7 Induces Anergy in Human CD4+ T Cells
Scientists found that engagement of Toll-like receptor (TLR)7 in CD4+ T cells induced intracellular calcium flux with activation of an anergic gene-expression program dependent on the transcription factor NFATc2, as well as unresponsiveness of T cells. [Nat Immunol] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Cigarette Smoking Impairs Human Pulmonary Immunity to Mycobacterium tuberculosis
Researchers compared the functional impairment, seen in human alveolar macrophages from non-smokers, smokers and ex-smokers, after infection with M. tuberculosis. [Am J Respir Crit Care Med]
Abstract | Press Release

Fc Gamma Receptor-TLR Cross-Talk Elicits Pro-Inflammatory Cytokine Production by Human M2 Macrophages
Scientists show that human M2 macrophages promote inflammation instead of suppressing inflammation on simultaneous exposure to complexed IgG and TLR ligands, as occurs in the context of diseases such as rheumatoid arthritis. [Nat Commun] Full Article

Selective Oral ROCK2 Inhibitor Down-Regulates IL-21 and IL-17 Secretion in Human T Cells via STAT3-Dependent Mechanism
The authors show that targeted rho-associated kinase 2 (ROCK2) inhibition down-regulates proinflammatory responses via concurrent regulation of STAT3/STAT5 phosphorylation and shifting Th17/Treg balance in human T cells with a minimal effect on the rest of the immune response. [Proc Natl Acad Sci USA]
Abstract | Full Article | Press Release

Tumor-Induced Senescent T Cells Promote the Secretion of Pro-Inflammatory Cytokines and Angiogenic Factors by Human Monocytes/Macrophages through a Mechanism that Involves Tim-3 and CD40L
Investigators report that tumor-induced senescent (TIS)-T cells may modulate monocyte activation. To gain insight into this interaction, CD4+ or CD8+TIS-T or control-T cells were co-incubated with autologous monocytes under inflammatory conditions. [Cell Death Dis] Full Article

C3d Adjuvant Effects Are Mediated through the Activation of C3d-Specific Autoreactive T Cells
C3d peptide sequences were previously synthesized and shown in vitro to bind multiple human leukocyte antigen (HLA)-DR alleles with high affinity, and induce interferon-γ responses in healthy donor peripheral blood mononuclear cells. Now investigators establish further correlations between HLA binding and HLA-specific lymphocyte reactions with select epitope clusters. [Immunol Cell Biol] Abstract

Glioblastoma Exosomes and IGF-1R/AS-ODN Are Immunogenic Stimuli in a Translational Research Immunotherapy Paradigm
In a pilot study, a vaccine consisting of Lucite diffusion chambers containing irradiated autologous tumor cells pre-treated with an antisense oligodeoxynucleotide directed against the insulin-like growth factor type 1 receptor was found to elicit positive clinical responses in 8/12 patients when implanted in the rectus sheath for 24 hours. Investigators make use of a murine glioma model and samples from glioblastoma patients in this second Phase I trial to investigate this novel therapeutic intervention more thoroughly. [Cancer Immunol Immunother]
Abstract | Press Release

Methylation of NKG2D Ligands Contributes to Immune System Evasion in Acute Myeloid Leukemia
Researchers demonstrate that DNA methylation can contribute to the absence of NKG2DL (natural killer group 2 member D ligand) expression during tumor progression. Treatment with demethylating agents restored the expression of NKG2DL on the cell surface of acute myeloid leukemia cells, leading to an enhanced recognition by NKG2D-expressing cells. [Genes Immun] Abstract

Dendritic Cell Reconstitution Is Associated with Relapse-Free Survival and Acute GvHD Severity in Children after Allogeneic Stem Cell Transplantation
The authors investigated the age- and sex-dependent immune reconstitution of myeloid and plasmacytoid DC in the peripheral blood of 45 children with leukemia or myelodysplastic syndrome after allo-SCT with regard to relapse, acute GvHD and relapse-free survival. [Bone Marrow Transplant] Abstract

Selective, Efficient Modulation of Activated CD4+ αβT Cells by the Novel Humanized Antibody GZ-αβTCR Targeting Human αβTCR
The novel humanized monoclonal antibody GZ-αβTCR, specific for the human αβT-cell receptor, was tested in vitro and in vivo for its specificity and efficacy to modulate the αβT-cell compartment. [Bone Marrow Transplant] Abstract

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How Ex Vivo Models Drive Progress in HIV Research: Read the Research Profiles
Molecular Regulation of Effector and Memory T Cell Differentiation
The authors underscore progress in delineating the underlying pathways that control diversification in T cell responses but also reveal gaps in the knowledge, as well as the challenges that arise in the application of this knowledge to rationally elicit desired T cell responses through vaccination and immunotherapy. [Nat Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the human immunology research field.
Analyses from Phase IIIb Study Provide Additional Data in Earlier Use of Orencia (Abatacept) Plus Methotrexate (MTX) in Citrullinated Protein (CCP)-Positive Adult Patients with Early Rheumatoid Arthritis (RA)
Bristol-Myers Squibb Company announced results of several new sub-analyses of the Phase IIIb AVERT trial that investigated the use of Orencia plus MTX in biologic and MTX-naïve CCP-positive early moderate to severe RA patients. [Press release from Bristol-Myers Squibb Company discussing research presented at the American College of Rheumatology (ACR) 2014 Annual Meeting, Boston] Press Release

Merck Announces Positive Study Investigating the Use of KEYTRUDA® (Pembrolizumab) Compared to Chemotherapy in Patients with Ipilimumab-Refractory Advanced Melanoma
Merck announced that a pre-specified analysis of investigational data from a pivotal Phase II study showed KEYTRUDA® substantially improved the primary endpoint of progression-free survival compared to chemotherapy in patients with ipilimumab-refractory advanced melanoma. [Press release from Merck & Co., Inc. discussing research presented at the Society of Melanoma Research (SMR) 2014 International Congress, Zurich] Press Release

Study Comparing Opdivo (Nivolumab) to Chemotherapy in Treatment Naïve Advanced Melanoma Patients Marks First PD-1 Immune Checkpoint Inhibitor to Demonstrate a Survival Benefit in a Phase III Trial
Bristol-Myers Squibb Company announced results from CheckMate-066, a Phase III randomized double blind study, comparing Opdivo, an investigational PD-1 immune checkpoint inhibitor, to the chemotherapy dacarbazine in patients with treatment naïve BRAF wild-type advanced melanoma. [Press release from Bristol-Myers Squibb Company discussing research presented at the Society of Melanoma Research (SMR) 2014 International Congress, Zurich] Press Release

Galena Biopharma Presents GALE-301 (Folate Binding Protein Immunotherapy) Phase IIa Clinical Trial Data
Galena Biopharma, Inc. announced that data from the company’s Phase I/IIa trial of GALE-301, a folate binding protein-derived immunotherapy, was presented. [Press release from Galena Biopharma, Inc. discussing research presented at the Society for Immunotherapy of Cancer (SITC) 29th Annual Meeting, National Harbor] Press Release

Phase II Clinical Data Support Immunotherapeutic Mechanism of Action of Peregrine Pharmaceuticals’ Bavituximab in Liver Cancer
Peregrine Pharmaceuticals, Inc. announced clinical and preclinical data related to the company’s immuno-oncology development program and its lead investigational immunotherapy drug candidate bavituximab. [Press release from Peregrine Pharmaceuticals, Inc. discussing research presented at the Society for Immunotherapy of Cancer’s (SITC) 29th Annual Meeting, National Harbor] Press Release

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Moffitt Cancer Center Announces Development of Experimental Treatment for Myelodysplastic Syndromes, Autoimmune Diseases
Moffitt Cancer Center announced the development of an innovative investigational biologic agent that could improve patient response and outcomes for MDS and other diseases. Moffitt and Celgene Corporation have entered into a licensing agreement that gives Celgene the exclusive rights to the novel, investigational myelodysplastic syndromes therapy. [Moffitt Cancer Center] Press Release

Protagen AG Signs Collaboration with QIAGEN to Develop Novel Protein Based Companion Diagnostics for Autoimmune Therapies
Protagen AG announced that it has entered into a long-term collaboration agreement with QIAGEN targeting the development of novel protein-based companion diagnostics for autoimmune disorders. [Protagen AG] Press Release

Pfizer Forms Global Strategic Alliance with Merck KGaA, Germany, to Jointly Develop and Commercialize Anti-PD-L1 to Accelerate Presence in Immuno-Oncology
Pfizer Inc. announced that it has entered into an agreement with Merck KGaA to jointly develop and commercialize MSB0010718C, an investigational anti-PD-L1 antibody currently in development by Merck KGaA as a potential treatment for multiple types of cancer. [Pfizer Inc.] Press Release

Genzyme’s Lemtrada Approved by the FDA
Genzyme announced that the U.S. Food and Drug Administration (FDA) has approved Lemtrada™ (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis. [Genzyme Corporation] Press Release

Cell Source’s Megadose Drug Combination Receives Regulatory Approval in Italy to Commence Human Clinical Trials
Cell Source, Inc. announced its Megadose Drug Combination has been cleared for human clinical trials in Italy. Cell Source’s proprietary Megadose Drug Combination is expected to increase bone marrow transplantation success and survival. [Cell Source, Inc. (PR Newswire Association LLC)] Press Release

Oncothyreon and Celldex Therapeutics Announce Initiation of Combination Immunotherapy Clinical Trial of ONT-10 and Varlilumab
Oncothyreon Inc. and Celldex Therapeutics, Inc. announced that they have initiated 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
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)
NEW The 4th NIF (Network of Immunology Frontier) Winter School on Advanced Immunology
January 18-23, 2015
Singapore, Singapore

NEW Keystone Symposium – Dendritic Cells and Macrophages Reunited
March 8-13, 2015
Montreal, Canada

Visit our events page to see a complete list of events in the human immunology community.
NEW Postdoctoral Scientist – Immunotherapy (Children’s Hospital of Eastern Ontario Research Institute)

NEW Research Scientist – Cancer and Inflammatory Diseases (Qu Biologics Inc.)

NEW Research Technician – Cancer and Inflammatory Diseases (Qu Biologics Inc.)

NEW Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant)

Research Associate – Interleukin-17 Producing T Cells in Rheumatic Disease (King’s College London)

Postdoctoral Position – Tumor Immunology (Cancer Research Center of Lyon)

PhD Studentship – Role of Mucus on the Impact of Gut Bacteria on Health (University of East Anglia)

Product Manager Global Marketing – Autoimmunity (Thermo Fisher Scientific)

Postdoctoral Position – Experimental Vascular Biology (Academic Medical Center)

PhD Studentship – Effects of Probiotics on Immunity in the Human Ageing Gut (University of East Anglia)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

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

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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