Human Immunology News Volume 2.46 | Dec 9 2014

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 FOXP3^–CD4⁺ 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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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 56^th 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 56^th 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 56^th 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 56^th American Society of Hematology (ASH) Annual Meeting, San Francisco] Press Release

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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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