Volume 3.15 | Apr 21

Human Immunology News 3.15 April 21, 2015
Human Immunology News
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Keytruda Shown to Improve Response to Tumors, Extend Lives of People with Advanced Melanoma
Keytruda® has signaled a paradigm shift in the way melanoma is treated. The drug is an antibody that blocks a protein called PD-1 that is expressed by immune cells. The protein puts the immune system’s brakes on, keeping its T cells from recognizing and attacking cancer cells. [Press release from UCLA’s Jonsson Comprehensive Cancer Center discussing publication in the New England Journal of Medicine]
Press Release | Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma
In this double-blind study involving 142 patients with metastatic melanoma who had not previously received treatment, doctors randomly assigned patients in a 2:1 ratio to receive ipilimumab combined with either nivolumab or placebo once every three weeks for four doses, followed by nivolumab or placebo every two weeks until the occurrence of disease progression or unacceptable toxic effects. [New Engl J Med]
Full Article | Press Release

COPA Mutations Impair ER-Golgi Transport and Cause Hereditary Autoimmune-Mediated Lung Disease and Arthritis
Expression of mutant COPA resulted in ER stress and the upregulation of cytokines priming for a T helper type 17 (TH17) response. Patient-derived CD4+ T cells also demonstrated significant skewing toward a TH17 phenotype that is implicated in autoimmunity. [Nat Genet] Abstract | Press Release

Homeostatic Regulation of T Cell Trafficking by a B Cell-Derived Peptide Is Impaired in Autoimmune and Chronic Inflammatory Disease
Investigators showed that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3 zeta delta protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. [Nat Med]
Abstract | Press Release

Induced Transcription and Stability of CELF2 mRNA Drives Widespread Alternative Splicing during T-Cell Signaling
Researchers demonstrated that expression of the splicing factor CELF2 (CUGBP, Elav-like family member 2) is regulated in response to T-cell signaling through combined increases in transcription and mRNA stability. They uncovered dozens of splicing events in cultured T cells whose changes upon stimulation are dependent on CELF2 expression, and provide evidence that CELF2 controls a similar proportion of splicing events during human thymic T-cell development. [Proc Natl Acad Sci USA] Abstract | Press Release

Targeting of Folate Receptor-Beta on Acute Myeloid Leukemia Blasts with Chimeric Antigen Receptor Expressing T Cells
The authors describe the development and evaluation of m909, the first chimeric antigen receptors (CARs) specific for human folate receptor beta (FRβ) in vitro and in vivo. m909 CAR T cells exhibited selective activation and lytic function against engineered C30-FRβ as well as endogenous FRβ+ acute myeloid leukemia cell lines in vitro. [Blood] Abstract

In Situ Delivery of Antigen to DC-SIGN+CD14+ Dermal Dendritic Cells Results in Enhanced CD8+ T Cell Responses
The authors showed using a human skin explant model that the in situ targeting of antigens to DC-SIGN using glycan-modified liposomes enhanced the antigen presenting capacity of CD14+ dermal DCs. [J Invest Dermatol] Abstract

VIP Boosts Regulatory T Cell Induction by Trophoblast Cells in an In Vitro Model of Trophoblast-Maternal Leukocyte Interaction
Investigators evaluated whether vasoactive intestinal peptide (VIP) produced by trophoblast cells induced regulatory T cells during the early interaction of maternal leukocytes with trophoblast cells, thus contributing to maternal tolerance. [J Leukoc Biol] Abstract

Delineation of a Novel Dendritic-Like Subset in Human Spleen
Human L-dendritic cells (DCs) were identified as a hCD11c+hCD11b+HLA-DR−hCD86+ subset in the spleen, along with the previously described subsets of hCD1c+ DCs, hCD123+ plasmacytoid DCs, hCD16+ DCs and hCD141+ DCs. Three subsets of monocytes were also characterized. [Cell Mol Immunol] Abstract

Microparticles Mediate Human Papillomavirus Type 6 or 11 Infection of Human Macrophages
Although macrophages are very important in antiviral immune responses, various types of viruses such as the human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human cytomegalovirus, and poliovirus are capable of infecting macrophages. However, the underlying mechanisms remain incompletely understood. [Cell Mol Immunol] Abstract

miR-20a Inhibits TCR-Mediated Signaling and Cytokine Production in Human Naïve CD4+ T Cells
Researchers found that miR-20a is rapidly induced upon TCR-triggering in primary human naïve CD4+ T cells and that its transcription is regulated in a Erk-, NF-κB-, and Ca++-dependent manner. [PLoS One] Full Article

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Chemokines, Their Receptors and Human Disease: The Good, the Bad and the Itchy
Aberrant expression or function of chemokines, or their receptors, has been linked to protection or susceptibility to specific infectious diseases, as well as the risk of autoimmune disease and malignancy, revealing critical roles of these molecules and their receptors in human health, disease and therapeutics. The authors focus on human diseases that provide lessons regarding the critical role of these specialized and complex cytokines. [Immunol Cell Biol] Full Article

The Importance of Co-Stimulation in the Orchestration of T Helper Cell Differentiation
Investigators outline the contribution of co-stimulatory and co-inhibitory receptors to the process of T helper cell differentiation, focusing on those pathways for which the underlying mechanisms are best known. [Immunol Cell Biol] Abstract

Tissue Resident Regulatory T Cells: Novel Therapeutic Targets for Human Disease
The authors summarize recent findings for visceral adipose tissue CD4+Foxp3+ regulatory T cells (Tregs), muscle Tregs, bone Tregs and skin memory Tregs, with a focus on their unique functions in local tissues. [Cell Mol Immunol] Abstract

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Celldex’s Varlilumab Demonstrates Synergistic Anti-Tumor Activity with PD-1 Signaling Blockade in Preclinical Studies
Celldex Therapeutics, Inc. announced preclinical results that further support varlilumab’s expansion into combination studies with PD-1 inhibitors. [Press release from Celldex Therapeutics, Inc. discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release | Poster

Data Presented Demonstrate Peregrine Pharmaceuticals’ Bavituximab Induces Immune Activation in PD-L1 Negative NSCLC Tumors
Peregrine Pharmaceuticals, Inc. announced the presentation of data from clinical translational studies of the company’s phosphatidylserine-targeting immunotherapy bavituximab. [Press release from Peregrine Pharmaceuticals, Inc. discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

Experimental Immune Therapy Tested in Preliminary Study of Women with Triple-Negative Breast Cancer
Early data in a preliminary human study show that an experimental immune system drug is generally safe and well tolerated in women with metastatic, triple-negative breast cancer, a persistently difficult form of the disease to treat. [Press release from Johns Hopkins Medicine discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

Immunotherapy Drug Pembrolizumab Shows Early Promise for Mesothelioma Patients
The PD-1 inhibitor pembrolizumab, a cancer immunotherapy drug, shrank or halted growth of tumors in 76 percent of patients with pleural mesothelioma, a rare and deadly form of cancer that arises in the outer lining of the lungs and internal chest wall. [Press release from Penn Medicine discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

Investigational Personalized Cellular Therapy Tolerated Well by Patients with Advanced Mesothelioma, Ovarian and Pancreatic Cancers
Genetically modified versions of patients’ own immune cells successfully traveled to tumors they were designed to attack in an early-stage trial for mesothelioma and pancreatic and ovarian cancers [Press release from Penn Medicine discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

First Randomized Study Evaluating Opdivo + Yervoy Regimen Demonstrates Superior Efficacy versus Yervoy Alone in Patients with Previously Untreated Advanced Melanoma
Bristol-Myers Squibb Company announced positive results from a Phase II trial, evaluating the Opdivo + Yervoy regimen versus Yervoy alone in patients with previously untreated advanced melanoma. [Press release from Bristol-Myers Squibb Company discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

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Curadev Announces Research Collaboration and Licensing Agreement to Develop Cancer Immunotherapeutic
Curadev Pharma Private Ltd. announced that it has entered into a research collaboration and exclusive license agreement with Roche for the development and commercialization of IDO1 and TDO inhibitors. [Curadev Pharma Private Ltd. (PR Newswire Association LLC)] Press Release

REGiMMUNE Announces Collaboration with JDRF and Pfizer Inc. for Type 1 Diabetes Prevention and Treatment Promoting Regulatory T-Cells
REGiMMUNE Corporation (RGI) and JDRF announced a partnership, along with financial assistance and scientific expertise from Pfizer Inc., for a research collaboration to develop an antigen-specific immunotherapy utilizing RGI’s proprietary αGalCer/liposome platform for immunological tolerance for the treatment of type 1 diabetes. [REGiMMUNE Corporation] Press Release

UNM Cancer Center Opens International Clinical Trial for Personalized Kidney Cancer Vaccine
The University of New Mexico (UNM) Cancer Center recently enrolled its first patient in a Phase III international clinical trial to test a personalized vaccine against metastatic kidney cancer. [University of New Mexico Cancer Center] Press Release

Imugene Files New HER-Vaxx Patent
Imugene Limited announced the filing of a new provisional patent titled, “A Vaccine Composition and Uses Thereof,” potentially extending HER-Vaxx patent life to 2036. [Imugene Limited] Press Release
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NEW Immune Profiling in Health and Disease
September 9-11, 2015
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Visit our events page to see a complete list of events in the human immunology community.
NEW Postdoctoral Position – Human Immune System Microbiota (Karolinska Institutet)

Postdoctoral Fellow – Mucosal Immunology and Mycobiome (Cedars-Sinai Medical Center)

Postdoctoral Position – Immunology (Institut Curie)

Associate Scientist – Immunology and Stem Cell Biology (Nerdbio Inc.)

Postdoctoral Position – Immunology (University of Oxford)

Postdoctoral Position – Immunology (Moffitt Cancer Center & Research Institute)

Postdoctoral Position – Immunology (New York University School of Medicine)

Research Officer – Immunology (Glenmark Pharmaceuticals S.A.)

Senior Research Officer – Immunology (Glenmark Pharmaceuticals S.A.)

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