Human Immunology News Volume 5.13 | Apr 4 2017

TOP STORY

Cytokine Receptor Signaling Is Required for the Survival of ALK⁻ Anaplastic Large Cell Lymphoma, Even in the Presence of JAK1/STAT3 Mutations

To investigate the clinical application of targeting Janus kinase (JAK) for anaplastic lymphoma kinase (ALK)⁻ anaplastic large cell lymphoma, scientists treated ALK⁻ cell lines of various histological origins with JAK inhibitors. Most exogenous cytokine-independent cell lines responded to JAK inhibition regardless of JAK mutation status. [Proc Natl Acad Sci USA] Abstract

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Identification of Autoreactive B Cells with Labeled Nucleosomes

Scientists propose a new flow cytometry technique for specific detection of anti-nucleosome B cells, which secrete autoantibodies in systemic lupus erythematosus, using labeled nucleosomes. They produced different fluorochrome-labeled nucleosomes, characterized them, and finally tested them in flow cytometry. [Sci Rep] Full Article

Systemic Frequencies of T Helper 1 and T Helper 17 Cells in Patients with Age-Related Macular Degeneration: A Case-Control Study

Researchers investigated the systemic differences in the frequency of T helper (Th)1 and Th17 cells in patients with non-exudative and exudative age-related macular degeneration and compared to age-matched controls. Flow cytometry was used to determine the systemic frequency of Th1 and Th17 cells, and percentage of CD4⁺ T-cells expressing CXCR3, IL12RB2, CCR6, IL23R, and co-expressing CXCR3 and CCR6. [Sci Rep] Full Article

Lipopolysaccharide-Elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14⁺ CD1c⁺ Monocytes

The authors demonstrated that thymic stromal lymphopoietin (TSLP) enhances human CD14⁺ monocyte CCL17 production in response to LPS and IL-4. Only a subset of CD14⁺ CD16⁻ monocytes, TSLPR⁺ monocytes, expressed TSLP receptor (TSLPR) complex upon LPS stimulation in an NF-κB- and p38-dependent manner. [J Immunol] Abstract

Hydrogen Peroxide Triggers a Dual Signaling Axis to Selectively Suppress Activated Human T Lymphocyte Migration

Investigators showed that low oxidative concentrations of H₂O₂ impede chemokinesis and chemotaxis of previously activated human T cells to CXCL11, but not CXCL10 or CXCL12. They showed that this deficiency in migration is due to a reduction in inflammatory chemokine receptor CXCR3 surface expression and cellular activation of lipid phosphatase SHIP-1. [J Immunol] Full Article

Higher Levels of IL-6, CD4 Turnover and Treg Frequency Are Already Present before cART in HIV-Infected Subjects with Later Low CD4 Recovery

Scientists selected pre-combined antiretroviral therapy (cART) samples of HIV-subjects with and without low CD4-recovery after cART. CD4 T-cell activation, senescence and exhaustion related markers were not found specifically altered before cART initiation. [Antiviral Res] Abstract

Synergistic Targeting of Breast Cancer Stem-Like Cells by Human γδ T Cells and CD8⁺ T Cells

To help develop novel immunotherapy approaches that efficiently target cancer stem cells (CSCs), an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC restricted γδ T cells and antigen-specific CD8⁺ T cells. [Immunol Cell Biol] Abstract | Full Article

Regulation of Cell Surface CB₂ Receptor during Human B Cell Activation and Differentiation

To better understand the pattern of cannabinoid receptor type 2 (CB₂) expression by human B cells, the authors examined CD20⁺ B cells from three tissue sources. Both surface and intracellular expression were present and uniform in cord blood B cells, where all cells exhibited a naïve mature phenotype. [J Neuroimmune Pharmacol] Abstract

LRRK2 Levels in Immune Cells Are Increased in Parkinson’s Disease

Researchers determined the expression pattern of leucine-rich repeat kinase 2 (LRRK2) in immune cell subsets and correlated it with the immunophenotype of cells from Parkinson’s disease and healthy subjects. [npj Parkinsons Dis] Full Article

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Mechanisms of Central Tolerance for B Cells

Single-cell antibody cloning has revealed defects of B cell central tolerance in human autoimmune diseases and in several human immunodeficiency diseases caused by single gene mutations, which indicates the relevance of B cell tolerance to disease and suggests possible genetic pathways that regulate tolerance. [Nat Rev Immunol] Abstract

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Eleven Biotherapeutics Presents New Preclinical Data Supporting the Potential of the Company’s Locally- and Systematically-Administered Drug Candidates

Eleven Biotherapeutics, Inc. announced new preclinical data with VB4-845, the active pharmaceutical ingredient used to formulate Vicinium™ and Proxinium™, and deBouganin, the de-immunized payload used in the company’s systemically-administered drug candidates. [Press release from Eleven Biotherapeutics, Inc. discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release | Poster

Kite Presents Ongoing Response Rate in Plenary Session from Its Pivotal CAR-T Trial of Axicabtagene Ciloleucel in Patients with Aggressive Non-Hodgkin Lymphoma

Kite Pharma, Inc. announced two plenary presentations of positive data from the primary analysis of ZUMA-1 for its lead CAR-T candidate, axicabtagene ciloleucel, in patients with refractory aggressive B-cell non-Hodgkin lymphoma. [Press release from Kite Pharma, Inc. discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

Oncodesign Presents its Latest Scientific Developments

Oncodesign presented its latest scientific developments. They presented four scientific posters on the radiotracer’s preclinical results, and on the latest developments designed to promote new drug discoveries. [Press release from Oncodesign discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

Siamab Therapeutics Presents New Preclinical Data for Its Novel Anti-STn Antibodies, Antibody-Drug Conjugates, and Anti-STn Bispecific Antibodies

Siamab Therapeutics, Inc. announced the presentation of two posters featuring new preclinical data for its novel anti-Sialyl-Tn (STn) antibodies, antibody-drug conjugates, and anti-STn, anti-CD3 bispecific antibodies. [Press release from Siamab Therapeutics, Inc. (Business Wire, Inc.) discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

Nektar Therapeutics Presents New Preclinical Data for Its Immuno-Oncology Programs

Nektar Therapeutics announced five preclinical data presentations for its immuno-oncology programs. [Press release from Nektar Therapeutics discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

Halozyme’s PEGPH20 Increases Immune Response and Effectiveness of Immunotherapies in Preclinical Cancer Models

Halozyme Therapeutics, Inc. demonstrated in preclinical models that its investigational drug PEGPH20 increases the number of cancer-fighting white blood cells accumulating in the tumor and the effectiveness of immunotherapies. [Press release from Halozyme Therapeutics, Inc. discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

OncoSec Presents Preclinical Data Demonstrating Improved Systemic Anti-Tumor Response following Modifications to IL-12 Gene Delivery Therapy

OncoSec Medical Incorporated presented a poster that included preclinical data demonstrating the latest developments of OncoSec’s gene delivery platform in a murine melanoma model. [Press release from OncoSec Medical Incorporated discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release | Abstract

IsoPlexis Collaboration Offers Breakthrough Insights into Detecting and Predicting Patient Response to T-Cell Therapy

Data captured by IsoCode, IsoPlexis Corporation’s single-cell precision engineering platform, detected a statistically significant association between the potency of CAR-T cell product prior to treatment and objective response of cancer patients post-treatment. [Press release from Isoplexis Corporation (PR Newswire Association LLC.) discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

Bristol-Myers Squibb Enters Collaboration to Leverage Foundation Medicine’s Molecular Information Platform to Identify Predictive Biomarkers across Multiple Tumor Types and Immunotherapy Agents

Bristol-Myers Squibb Company and Foundation Medicine announced a collaboration that leverages Foundation Medicine’s comprehensive genomic profiling and molecular information solutions to identify predictive biomarkers such as Tumor Mutational Burden and Microsatellite Instability in patients enrolled across clinical trials investigating Bristol-Myers Squibb’s cancer immunotherapies. [Bristol-Myers Squibb Company] Press Release

Novel 3D Cell-Based Assays Accelerate Discovery for Immuno-Oncology/CAR-T Therapies

InSphero AG highlighted the unique advantages of its physiologically relevant 3D InSight™ Microtissue Platform to drive more efficient development of anti-cancer drugs and immuno-oncology approaches. [InSphero AG] Press Release

Sorrento Therapeutics Anti-CEA CAR-T Demonstrates Promising Clinical Activity and Safety in Phase Ib Clinical Trial

Sorrento Therapeutics, Inc. and its cellular therapy focused subsidiary, TNK Therapeutics, Inc., announced the results from the Hepatic ImmunoTherapy for Metastases-Selective Internal Radiation Therapy Study, a Phase Ib single arm trial testing its anti-CEA CAR-T administered regionally by hepatic artery infusion followed by selective internal radiation therapy in heavily pre-treated patients with CEA positive liver metastases. [Sorrento Therapeutics, Inc.] Press Release

Nektar Therapeutics Initiates Clinical Study of NKTR-358, a First-in-Class Regulatory T Cell Stimulator, Being Developed for the Treatment of Immune and Inflammatory Disorders

Nektar Therapeutics announced that it has begun dosing in a Phase I clinical study evaluating NKTR-358, the company’s new biologic therapy, which is being developed to treat a wide range of auto-immune diseases and inflammatory disorders. NKTR-358 selectively stimulates the growth and activation of regulatory T cells in the body in order to restore the body’s self-tolerance mechanisms. [Nektar Therapeutics] Press Release

Novartis Announces First CAR-T Cell Therapy BLA for Pediatric and Young Adult Patients with r/r B-Cell ALL Granted FDA Priority Review

Novartis announced that the US Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) filing and granted priority review for CTL019, an investigational chimeric antigen receptor T cell (CAR-T) therapy, in relapsed and refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). [Novartis AG] Press Release

Kite Completes Submission of U.S. Biologics License Application (BLA) for Axicabtagene Ciloleucel as the First CAR-T Therapy for the Treatment of Patients with Aggressive Non-Hodgkin Lymphoma (NHL)

Kite Pharma, Inc. announced that it has completed the rolling submission with the U.S. Food and Drug Administration of the BLA for axicabtagene ciloleucel as a treatment for patients with relapsed or refractory aggressive NHL who are ineligible for autologous stem cell transplant. [Kite Pharma, Inc.] Press Release

Kiadis Pharma Announces Positive Regulatory Update on ATIR101™ and ATIR201™

Kiadis Pharma N.V. announced that it has obtained regulatory approval from the national authority in Belgium to start its randomized, controlled, transatlantic Phase III clinical trial with ATIR101™ for acute leukemia in Belgium. [Kiadis Pharma N.V.] Press Release

Brazilian Scientists Reeling as Federal Funds Slashed by Nearly Half

Brazilian scientists have been left horrified by a 44% slash to the federal science budget, announced by the country’s government. This will leave the Ministry of Science, Technology, Innovations and Communications with its lowest budget in at least 12 years at just 2.8 billion reais, equivalent to US$898 million — a 2.2 billion reais cut from the 5 billion reais of funding that the government had originally proposed for 2017. [Nature News] Editorial

Genetic Details of Controversial ‘Three-Parent Baby’ Revealed

When a US fertility clinic revealed last year that it had created a baby boy using a controversial technique that mixes DNA from three people, scientists were quick to raise the alarm. Some objected on ethical grounds, and others questioned the scientific claims made by the clinic’s leader, physician John Zhang. [Nature News] Editorial

Few U.S. Animal Inspections Are Being Posted

The Donald Trump administration appears to have reversed its decision to remove from public sight the results of past government inspections of animal research facilities. But getting hold of new inspection reports is proving to be another matter. An animal welfare researcher has found that only four reports have been posted during the first quarter of 2017. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Phagocytes
June 11-16, 2017
Waterville Valley, United States

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NEW Research Assistant – Immunology (University of Cambridge)

Research Technologist – Cell Separation & Immunology (STEMCELL Technologies, Inc.)

Postdoctoral Fellow Position – Translational Immunology (The University of Utah)

Postdoctoral Research Fellowship – Tumor Immunology (University of Oslo)

Postdoctoral Fellow – Stromal Tissues Imprinting of Immune Cell Function (AstraZeneca)

Postdoctoral Fellow – Immune-Oncology (Johnson and Johnson)

Postdoctoral Researcher – Development of Immune System (Lund University)

Research Investigator – Immuno-Oncology (Bristol-Meyers Squibb)

Postdoctoral Position – Interaction between the Immune System and Pancreatic Cancer (Cold Spring Harbor Laboratory)

Postdoctoral Fellow – Immune Regulation and Human Diseases (The Wistar Institute)

Bioinformatician – Immunology (KOTAI Biotechnologies, Inc.)

Assistant Associate – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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