Human Immunology News Volume 2.25 | Jul 8 2014

p53MVA Therapy in Patients with Refractory Gastrointestinal Malignancies Elevates p53-Specific CD8⁺ T Cell Responses
Scientists conducted a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in patients with refractory gastrointestinal cancers. Peripheral blood samples were collected pre- and post-immunization for immunophenotyping, monitoring of p53MVA induced immune response and examination of PD-1 checkpoint inhibition in vitro. [Clin Cancer Res] Abstract

Induced CD8⁺FOXP3⁺ Regulatory T Cells in Rheumatoid Arthritis Are Modulated by p38 Phosphorylation and Monocytes Expressing Membrane TNF-α and CD86
Researchers determined the suitability of repurposing anti-CD3 monoclonal antibody therapy for rheumatoid arthritis by analyzing its ability to induce CD8⁺FOXP3⁺ regulatory T cells from peripheral blood cells. [Arthritis Rheumatol] Abstract

The Majority of Human Memory B Cells Recognizing RhD and Tetanus Resides in IgM⁺ B Cells
Scientists previously observed that anti-RhD (D) Igs cloned from two donors, hyperimmunized with D⁺ erythrocytes, were predominantly of the IgM isotype. They analyzed the phenotype and frequency of D- and tetanus toxoid-specific B cells by culturing B cells in limiting dilution upon irradiated CD40L-expressing EL4.B5 cells and testing the culture supernatant. [J Immunol] Abstract | Full Article

Surface Expression of CD39 Identifies an Enriched Treg-Cell Subset in the Rheumatic Joint, which Does Not Suppress IL-17A Secretion
As expression of the ATP-hydrolyzing enzymes CD39 and CD73 and the resulting anti-inflammatory adenosine production have been implicated as an important mechanism of suppression, researchers characterized FOXP3⁺ regulatory T (Treg) cells in blood and synovial fluid samples of rheumatoid arthritis patients in the context of CD39 and CD73 expression. [Eur J Immunol] Abstract

The Immunomodulatory Effects of Human Mesenchymal Stem Cells on Peripheral Blood Mononuclear Cells in ALS Patients
Researchers investigated the immunomodulatory effect of mesenchymal stem cells on peripheral blood mononuclear cells in amyotrophic lateral sclerosis (ALS) patients, focusing on regulatory T lymphocytes (CD4⁺/CD25^high/FoxP3⁺) and the mRNA expression of several cytokines. [J Neurochem] Abstract

Therapeutic DC Vaccination with IL-2 as a Consolidation Therapy for Ovarian Cancer Patients: A Phase I/II Trial
Ten ovarian cancer patients with minimal residual disease were treated with autologous dendritic cells (DCs) and IL-2 to evaluate the safety and feasibility of this therapeutic strategy and to characterize the antigen-specific immune alterations induced through this treatment. [Cell Mol Immunol] Abstract

Impaired T Cell Activation and Cytokine Production by Calcitriol-Primed Human B Cells
Researchers studied whether calcitriol-primed B cells modulate T activation and function. After removal of calcitriol, primed B cells were cocultured with autologous CD4⁺ T cells. Besides the B cell phenotype T cell activation and their consecutive cytokine production were assessed. [Clin Exp Immunol] Abstract

Comparison of Different Rabbit ATG Preparation Effects on Early Lymphocyte Subset Recovery after Allogeneic HSCT and Its Association with EBV-Mediated PTLD
Scientists conclude that high, but importantly not currently applied low dosages of antithymocyte globulin-Genzyme (ATG-G), impair thymic T cell regeneration and memory T cell immunity to a greater extent than ATG-Fresenius in pediatric patients. In addition, results suggest an increased risk for Epstein-Barr virus (EBV)-mediated post-transplant lymphoproliferative disorder (PTLD) when treated with ATG-G. [J Cancer Res Clin Oncol] Abstract

Regulation of Hematopoietic and Leukemic Stem Cells by the Immune System
Paradoxically, many immune mechanisms that evolved to activate emergency hematopoiesis during infection may actually contribute to the expansion and differentiation of leukemic stem cells (LSCs), promoting leukemia progression. The authors summarize mechanisms by which the immune system regulates hematopoietic stem cells and LSCs. [Cell Death Diff] Full Article

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CEL-SCI Receives Regulatory Clearance to Expand CEL-SCI’s Phase III Head and Neck Cancer Trial into Austria
CEL-SCI Corporation announced that it has received regulatory clearance from the Austrian Federal Office for Safety in Health Care to begin patient enrollment in the company’s Phase III head and neck cancer clinical trial of its investigational cancer immunotherapy treatment Multikine (Leukocyte Interleukin, Injection). [CEL-SCI Corporation] Press Release

Novartis Personalized Cell Therapy CTL019 Receives FDA Breakthrough Therapy Designation
Novartis announced that the United States Food and Drug Administration (FDA) has granted Breakthrough Therapy status to CTL019, an investigational chimeric antigen receptor therapy for the treatment of pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia. [Novartis AG] Press Release

Glenmark’s Novel Monoclonal Antibody GBR 830 for Treatment of Autoimmune Diseases Entering Human Trials
Glenmark Pharmaceuticals S.A. announced that GBR 830, a novel monoclonal antibody is entering human trials. GBR 830 is a pure antagonist of OX40, a co-stimulatory receptor expressed on T cells mediating T cell activation and survival. [Glenmark Pharmaceuticals S.A. (PR Newswire Association LLC)] Press Release

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