Human Immunology News Volume 4.09 | Mar 8 2016

Melanoma Cell Lysosome Secretory Burst Neutralizes the CTL-Mediated Cytotoxicity at the Lytic Synapse
Researchers showed that, on conjugation with CD8⁺ cytotoxic T lymphocytes (CTLs), human melanoma cells undergo an active late endosome/lysosome trafficking, which is intensified at the lytic synapse and is paralleled by cathepsin-mediated perforin degradation and deficient granzyme B penetration. Abortion of SNAP-23-dependent lysosomal trafficking, pH perturbation or impairment of lysosomal proteolytic activity restores susceptibility to CTL attack. [Nat Commun] Full Article

Circulating T Follicular Helper Cells with Increased Function during Chronic Graft-versus-Host-Disease
Investigators performed extensive phenotypic and functional analysis of circulating T follicular helper (cTFH) and B cells in 66 patients after hematopoietic stem cell transplantation. Patients with active chronic graft-versus-host disease (GvHD) had significantly lower frequency of cTFH compared to patients without chronic GvHD. [Blood] Abstract

Local Delivery of CpG-B and GM-CSF Induces Concerted Activation of Effector and Regulatory T Cells in the Human Melanoma Sentinel Lymph Node
Scientists previously described the combined administration of DC-targeting agents to result in activation and recruitment of potentially cross-presenting BDCA3⁺ DCs to the sentinel lymph node. In this report they describe the effects on effector and regulatory T and NK cell subsets. [Cancer Immunol Immunother] Full Article

Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1
Investigators report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Two patients developed BP while receiving the anti-programmed death 1 (PD-1) monoclonal antibody (mAb) nivolumab, and one while receiving the anti-PD-L1 mAb durvalumab. [Cancer Immunol Res] Abstract

Immune Responses to the Cancer Testis Antigen XAGE-1b in Non-Small Cell Lung Cancer Caucasian Patients
Researchers assessed spontaneous immune responses to XAGE-1b, a tumor specific antigen of the cancer testis antigen group that has been previously reported to be spontaneously immunogenic in the Japanese population, in a cohort of Caucasian patients with non-small cell lung cancer. [PLoS One] Full Article

Suppressor Properties of Human CD8⁺CD28^– T Cells in Mixed Leukocyte Reaction Are Not Affected by CsA and RAPA
Investigators evaluated the influence of the immunosuppressive drugs cyclosporine A (CsA) and rapamycin (RAPA) on the level, suppressor properties, and phenotype of human CD8⁺CD28⁻ T cells in vitro. [Arch Immunol Ther Exp] Abstract

AIRE Is Not Essential for the Induction of Human Tolerogenic Dendritic Cells
In Autoimmune Regulator (AIRE)-deficient patients and healthy controls, scientists validated the role of AIRE in the generation and function of monocyte-derived immunogenic/inflammatory dendritic cells (DCs) and tolerogenic DCs by determining mRNA and protein expression of AIRE and comparing activation markers, cytokine production and T-cell stimulatory capacity of AIRE⁺ and AIRE^– DCs. [Autoimmunity] Abstract

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Top-Line Data from All Patients on the Primary Endpoint of Kiadis Pharma’s Phase II Trial with ATIR101™ Selected for Oral Presentation
Kiadis Pharma N.V. announced that key data from the company’s ongoing single-dose Phase II clinical trial with its lead product ATIR101™ has been selected for an oral presentation to discuss the top-line data. [Press release from the Kiadis Pharma N.V. discussing research to be presented at the 42^nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Valencia] Press Release

Advaxis Study in Head and Neck Cancer Selected for Late-Breaking Poster
Advaxis, Inc. announced that data from a Phase II study of its lead Lm immunotherapy candidate in HPV-associated head and neck cancer, axalimogene filolisbac, has been selected as a late-breaker poster presentation. [Press release from Advaxis, Inc. discussing research to be presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, New Orleans] Press Release

Ixekizumab Demonstrates Rapid, Clinically Meaningful Improvements as Early as One Week among Patients with Moderate-to-Severe Plaque Psoriasis
Eli Lilly and Company announced that treatment for moderate-to-severe plaque psoriasis with ixekizumab resulted in clinically meaningful improvements as early as one week, compared to patients treated with etanercept or placebo. [Press release from Eli Lilly and Company discussing research presented at the 74^th American Academy of Dermatology (AAD) Annual Meeting, Washington, D.C.] Press Release

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Genmab Provides Update on Ofatumumab Development in Autoimmune Indications
Genmab A/S announced an update on development plans for ofatumumab in autoimmune indications focusing on relapsing multiple sclerosis following the transfer of the rights to ofatumumab in this disease area from GlaxoSmithKline to Novartis at the end of 2015. [Genmab A/S] Press Release

Immunomedics Develops Novel Antibody-Based Products for Autoimmune Disease and Cancer Therapy
Immunomedics, Inc. announced the issuance of U.S. patent no. 9,278,129 for the company’s new patent family “Methods of Treating Rapidly Progressive Glomerulonephritis Using Chimeric and Humanized Anti-Histone Antibodies.” [Immunomedics, Inc.] Press Release

True North Therapeutics Launches COMPASS Registry to Advance Development of New Therapeutics for Patients with Cold Agglutinin Disease (and Other Autoimmune Hemolytic Anemias)
True North Therapeutics announced the launch of the COMPASS Registry, a patient registry created by True North Therapeutics in collaboration with PatientCrossroads, for patients with cold agglutinin disease (CAD). The COMPASS Registry is designed to build a deeper understanding of the natural history of CAD, characterize clinical biomarkers and engage early with patients and physicians to help accelerate development of new therapeutics. [True North Therapeutics, Inc.] Press Release

Xencor Initiates Two Phase II Trials of XmAb5871 in IgG4-Related Disease and Systemic Lupus Erythematosus
Xencor, Inc. announced dosing the first patient in a Phase II trial of XmAb^®5871 in patients with IgG4-related disease. The company also announced dosing the first patient in a Phase II trial of XmAb5871 in patients with systemic lupus erythematosus. [Xencor, Inc.] Press Release

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Tenure-Track Position – Immunology (Massachusetts General Hospital)

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