Volume 2.46 | Dec 9

Human Immunology News 2.46 December 9, 2014
Human Immunology News
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Protein Predicts Response to New Immunotherapy Drug
The presence of an immune-suppressing protein in non-cancerous immune cells may predict how patients with different types of cancer respond to treatment. [Press release from Yale University discussing online prepublication in Nature] Press Release | Abstract
How Ex Vivo Models Drive Progress in HIV Research: Read the Research Profiles
PUBLICATIONS (Ranked by impact factor of the journal)
PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin’s Lymphoma
Researchers hypothesized that nivolumab, a programmed death 1 (PD-1)-blocking antibody, could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin’s lymphoma. [New Engl J Med]
Full Article | Press Release | Video

Functional Heterogeneity of Human Memory CD4+ T Cell Clones Primed by Pathogens or Vaccines
By combining antigenic stimulation and T cell receptor deep sequencing, researchers show that human pathogen- and vaccine-specific T helper 1 (Th1), Th2 and Th17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. [Science] Abstract

High-Throughput Detection of miRNAs and Gene-Specific mRNA at the Single-Cell Level by Flow Cytometry
Scientists describe optimized protocols that exploit a highly sensitive fluorescent in situ hybridization method based on branched DNA technology to detect mRNA and miRNA in human leukocytes. [Nat Commun]
Abstract | Press Release

The Antimicrobial Peptide ​LL37 Is a T-Cell Autoantigen in Psoriasis
Investigators found that two-thirds of patients with moderate-to-severe plaque psoriasis harbor ​CD4+ and/or CD8+ T cells specific for ​LL37, an antimicrobial peptide overexpressed in psoriatic skin and reported to trigger activation of innate immune cells. [Nat Commun] Abstract

Human Regulatory T-Cell Development Is Dictated by Interleukin-2 and -15 Expressed in a Non-Overlapping Pattern in the Thymus
Scientists investigated the role of common gamma-chain cytokines in human thymus-derived FOXP3-expressing regulatory T-cells differentiation by performing gain- and loss-of-function experiments in 3D and 2D postnatal thymic cultures. [J Autoimmun] Abstract

Anti-CD33 Chimeric Antigen Receptor Targeting of Acute Myeloid Leukemia
Researchers generated a second generation CD33-specific chimeric antigen receptor capable of redirecting cytolytic effector T cells against leukemic cells. Chimeric antigen receptor-modified T cells efficiently killed leukemia cell lines and primary tumor cells in vitro. [Haematologica] Abstract | Full Article

T-Cell Receptor Sequencing Reveals the Clonal Diversity and Overlap of Colonic Effector and FOXP3+ T Cells in Ulcerative Colitis
To see if human FOXP3+ lamina propria (LP) T cells are an activated fraction of otherwise FOXP3 effector T cells and explore their clonal diversity in health and disease, investigators deep sequenced clonally unique T-cell receptor hypervariable regions of FOXP3+ and FOXP3CD4+ T-cell subpopulations from inflamed versus noninflamed colon LP or mesenteric lymph nodes of patients with or without ulcerative colitis. [Inflamm Bowel Dis] Abstract

Ex Vivo-Expanded but Not In Vitro-Induced Human Regulatory T Cells Are Candidates for Cell Therapy in Autoimmune Diseases Thanks to Stable Demethylation of the FOXP3 Regulatory T Cell-Specific Demethylated Region
Investigators undertook a systematic comparison of human expanded regulatory T cells (Tregs) and induced Tregs to find which was the most suitable for clinical implementation, and then tested their effectiveness and feasibility in rheumatoid arthritis. [J Immunol] Abstract

Differential Expression of the Immunosuppressive Enzyme IL4I1 Induce Aiolos+, but Not Natural Helios+, FOXP3+ Treg Cells
Scientists previously identified a population of human FOXP3+ Treg cells that secrete IL-17 ex vivo; here, they address the expression of IL4I1 in that Treg-cell population. [Eur J Immunol] Abstract

Human Mesenchymal Stromal Cells Enhance the Immunomodulatory Function of CD8+CD28 Regulatory T Cells
Investigators studied the effects of mesenchymal stromal cells (MSCs) on CD8+CD28 regulatory T (Treg) cells and found that the MSCs could not only increase the proportion of CD8+CD28 T cells, but also enhance CD8+CD28 T cells’ ability of hampering naive CD4+ T-cell proliferation and activation, decreasing the production of IFN-γ by activated CD4+ T cells and inducing the apoptosis of activated CD4+ T cells. [Cell Mol Immunol] Full Article

Inactivation of Notch Signaling Reverses the Th17/Treg Imbalance in Cells from Patients with Immune Thrombocytopenia
In vitro, investigators treated peripheral blood mononuclear cells from immune thrombocytopenia and healthy controls with γ-secretase inhibitor (DAPT). They demonstrate that DAPT was effective in inhibiting mRNA expression of Notch signaling molecules. [Lab Invest] Abstract

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Crosstalk at the Mucosal Border: Importance of the Gut Microenvironment in IBS
This review highlights the crosstalk between the gut microbiota, the enteroendocrine system, the immune system and the role of intestinal permeability in patients with IBS. [Nat Rev Gastroenterol Hepatol] Abstract

Visit our reviews page to see a complete list of reviews in the human immunology research field.
Penn Medicine Researchers Announce Latest Results of Investigational Cellular Therapy CTL019
The latest results of clinical trials of more than 125 patients testing an investigational personalized cellular therapy known as CTL019 were presented. [Press release from Penn Medicine discussing research presented at the 56th American Society of Hematology (ASH) Annual Meeting, San Francisco] Press Release

Benefits Persist in T Cell Therapy for Children with Relapsed Leukemia
An innovative cell therapy against a highly aggressive form of acute lymphoblastic leukemia continues to show highly promising results in children treated in a pilot study. [Press release from Children’s Hospital of Philadelphia discussing research presented at the 56th American Society of Hematology (ASH) Annual Meeting, San Francisco] Press Release

Studies Led by Memorial Sloan Kettering Investigators Show Immunotherapy Drugs Improve Outcomes in Hodgkin Lymphoma Patients
For classical Hodgkin lymphoma patients, two Phase I studies are already demonstrating dramatic results. [Press release from Memorial Sloan Kettering Cancer Center discussing research presented at the 56th American Society of Hematology (ASH) Annual Meeting, San Francisco] Press Release

Data Investigating KEYTRUDA® (Pembrolizumab), Merck’s Anti-PD-1 Therapy, in Patients with Classical Hodgkin Lymphoma Presented
Merck announced early study findings demonstrating that KEYTRUDA® achieved an overall response rate of 66 percent in transplant-ineligible and failure patients with relapsed/refractory classical Hodgkin lymphoma. [Press release from Merck & Co., Inc. discussing research presented at the 56th American Society of Hematology (ASH) Annual Meeting, San Francisco] Press Release

Amgen Announces New Data from Phase II BLINCYTO™ (Blinatumomab) Immunotherapy Study in Patients with Acute Lymphoblastic Leukemia and Minimal Residual Disease
Amgen announced new data from the Phase II BLAST study which evaluated the bispecific T cell engager immunotherapy BLINCYTO™ in patients with minimal residual disease positive B-cell precursor acute lymphoblastic leukemia. [Press release from Amgen Inc. discussing research presented at the 56th American Society of Hematology (ASH) Annual Meeting, San Francisco] Press Release

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Juno Therapeutics Executes License for Phase I CAR-T Product Candidate Targeting CD22 for Hematological Malignancies
Juno Therapeutics, Inc. announced that it has entered into an agreement to obtain a license from Opus Bio, Inc. for a CAR-T cell product candidate targeting CD22, a protein expressed on most B cell leukemias and lymphomas. [Juno Therapeutics, Inc.] Press Release

Advaxis Announces FDA Acceptance of Its Investigational New Drug Application to Commence Clinical Trials of ADXS-PSA in Combination with Merck’s KEYTRUDA® (Pembrolizumab) for Prostate Cancer
Advaxis, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug application to conduct a Phase I/II clinical study to evaluate the combination of ADXS-PSA with KEYTRUDA® in patients with previously treated metastatic castration-resistant prostate cancer. [Advaxis, Inc.] Press Release

CEL-SCI Expands Its Pivotal Phase III Immunotherapy Head and Neck Cancer Trial with Addition of Seven More Clinical Sites
CEL-SCI Corporation announced that it has added seven new clinical sites to its global pivotal Phase III head and neck cancer trial for its investigational immunotherapy Multikine. [CEL-SCI Corporation] Press Release

VAXIMM Reports Positive Follow-On Data from Oral Cancer Vaccine Trial
VAXIMM AG announced follow-on data from the first clinical trial of its investigational oral T-cell vaccine VXM01. [VAXIMM AG] Press Release
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NEW Keystone Symposium – Host Response in Tuberculosis
January 22-27, 2015
Santa Fe, United States

NEW IMMUNOLOGY 2015™: The American Association of Immunologists (AAI) Annual Meeting
May 8-12, 2015
New Orleans, United States

NEW The 2nd Gene and Immunotherapy Conference in Vietnam
September 19-20, 2015
Ho Chi Minh City, Vietnam

Visit our events page to see a complete list of events in the human immunology community.
NEW Postdoctoral Research Associate – Immunology (University of Edinburgh)

Investigator – Gut Mucosal Immunology Research (Novartis Institutes for BioMedical Research)

Senior Research Fellow – Immune Response in Aging/Persistent Infections (Singapore Immunology Network A*STAR)

Faculty Position – Department of Microbiology and Immunology (Indiana Univeristy School of Medicine)

Postdoctoral Position – Mucosal Immunology (Karolinska Institute)

Postdoctoral Fellow – Immunology (Hospital for Special Surgery)

Postdoctoral Fellow – Translational Medicine and Tumor Immunology (Medical University of Warsaw)

Product Manager Global Marketing – Autoimmunity (Thermo Fisher Scientific)

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.)

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