Human Immunology News Volume 3.10 | Mar 17 2015

Mutational Landscape Determines Sensitivity to PD-1 Blockade in Non-Small Cell Lung Cancer
Scientists used whole-exome sequencing of non-small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors associated with improved objective response, durable clinical benefit, and progression-free survival. [Science] Abstract | Press Release | Video

Anti-IL-23A mAb BI 655066 for Treatment of Moderate-to-Severe Psoriasis: Safety, Efficacy, Pharmacokinetics, and Biomarker Results of a Single-Rising-Dose, Randomized, Double-Blind, Placebo-Controlled Trial
BI 655066 is a fully human IgG₁ mAb specific for the IL-23 p19 subunit. This first-in-human proof-of-concept study evaluated the clinical and biological effects of BI 655066 in patients with moderate-to-severe plaque psoriasis. [J Allergy Clin Immunol] Abstract | Press Release

The ​Interferon-Related Developmental Regulator 1 Is Used by Human Papillomavirus to Suppress NFκB Activation
Using non-infected and freshly established or persistent hrHPV-infected keratinocytes researchers showed that high-risk human papillomavirus impaired the acetylation of NFκB/​RelA K310 in keratinocytes. As a consequence, keratinocytes display a decreased pro-inflammatory cytokine production and immune cell attraction in response to stimuli of the innate or adaptive immune pathways. [Nat Commun] Full Article

Reprogramming of Primary Human Philadelphia Chromosome-Positive B Cell Acute Lymphoblastic Leukemia Cells into Nonleukemic Macrophages
Investigators found that primary human BCR-ABL1⁺ precursor B-cell acute lymphoblastic leukemia cells could be induced to reprogram into macrophage-like cells by exposure to myeloid differentiation-promoting cytokines in vitro or by transient expression of the myeloid transcription factor C/EBPα or PU.1. [Proc Natl Acad Sci USA] Abstract | Press Release

Tim-3 Protects Decidual Stromal Cells from Toll-Like Receptor-Mediated Apoptosis and Inflammatory Reactions and Promotes Th2 Bias at the Maternal-Fetal Interface
Researchers demonstrated significantly lowered expression of T-cell immunoglobulin and mucin domain 3 (Tim-3) in miscarried decidual stromal cells, indicating that Tim-3 might play important roles in maintaining successful pregnancies. [Sci Rep] Full Article

Heterozygosity for the Common Perforin Mutation, p.A91V, Impairs the Cytotoxicity of Primary Natural Killer Cells from Healthy Individuals
Researchers investigated the function of p.A91V on a wild-type perforin background. They demonstrated that the p.A91V mutation results in protein misfolding and an appreciable reduction in natural killer cell cytotoxicity in healthy carriers of p.A91V. [Immunol Cell Biol] Abstract

A New Effect of IL-4 on Human γδ T Cells: Promoting Regulatory Vδ1 T Cells via IL-10 Production and Inhibiting Function of Vδ2 T Cells
Scientists investigated the effects of interleukin 4 (IL-4) on the activation and proliferation of γδ T cells and the balance between variable delta 1 (Vδ1) and Vδ2 T cells in humans. The results showed that IL-4 inhibited the activation of γδ T cells in the presence of γδ T-cell receptor stimulation in a STAT6-dependent manner. [Cell Mol Immunol] Abstract

Clinical Testing of a Dendritic Cell Targeted Therapeutic Vaccine in Patients with Chronic Hepatitis C Virus Infection
Due to the central role that dendritic cells (DC) play in the activation of T-cell responses, scientists aimed to carry out a therapeutic vaccination clinical trial in hepatitis C virus patients using DC. [Mol Ther Methods Clin Dev] Full Article

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Inflammation in the Mouth and Joints in Rheumatoid Arthritis
Sheila Arvikar, Massachusetts General Hospital, presented a study titled, “Inflammation in the Mouth and Joints in Rheumatoid Arthritis.” [Press release from the International Association for Dental Research (IADR) discussing research presented at the 93^rd General Session and Exhibition of the IADR, Boston] Press Release

Immunicum’s Chief Scientific Officer Presented the Technology behind the Cancer Vaccine INTUVAX
Immunicum AB announced that the company’s Chief Scientific Officer, Dr. Alex Karlsson-Parra, has presented the technology behind the cancer vaccine INTUVAX. [Press release from Immunicum AB discussing research presented at the Symposium on Breakthroughs in Clinical & Translational Immunology, Stockholm] Press Release

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Cell Medica Collaborates with Cell Therapy Catapult to Help Bring Its New Treatment to NHS
The Cell Therapy Catapult and Cell Medica announced a collaboration to accelerate NHS adoption of Cell Medica’s Cytovir™ CMV. Cytovir™ CMV is an individualized immune cell therapy that involves the infusion of immune cells from a donor into an immunosuppressed patient, in order to reconstitute their immunity to cytomegalovirus (CMV). [Cell Therapy Catapult] Press Release

New Immunotherapy Drug ‘Fast-Tracked’ for Melanoma Patients
A new immunotherapy drug, pembrolizumab, has become the first treatment ‘fast-tracked’ for NHS patients with advanced melanoma. Clinical trials have shown that it has the potential to ease symptoms and extend survival. [Cancer Research UK] Press Release

VAXIL Receives EU Orphan Drug Designation for ImMucin for the Treatment of Multiple Myeloma
Vaxil Bio reports that its lead drug candidate, ImMucin has received orphan drug designation from the European Medicines Agency of the European Commission for the treatment of multiple myeloma. [Vaxil BioTherapeutics Ltd.] Press Release

MacroGenics Initiates Phase I Study of MGD010 for the Treatment of Autoimmune Disorders
MacroGenics, Inc. announced the initiation of a Phase I study with MGD010, its first dual-affinity re-targeting (DART^®) molecule being developed for patients with autoimmune disorders. [MacroGenics, Inc.] Press Release

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