Human Immunology News Volume 2.40 | Oct 21 2014

PCSK9 Is a Critical Regulator of the Innate Immune Response and Septic Shock Outcome
The authors show that reduced proprotein convertase subtilisin/kexin type 9 (PCSK9) function is associated with increased pathogen lipid clearance via the low-density lipoprotein receptor, a decreased inflammatory response, and improved septic shock outcome. [Sci Transl Med] Abstract | Press Release

‘Division of Labor’ in Response to Host Oxidative Burst Drives a Fatal Cryptococcus gattii Outbreak
Investigators show that a subpopulation of intracellular C. gattii adopts a tubular mitochondrial morphology in response to host reactive oxygen species. These fungal cells then facilitate the rapid growth of neighboring C. gattii cells with non-tubular mitochondria, allowing for effective establishment of the pathogen within a macrophage intracellular niche. [Nat Commun] Full Article | Press Release

Characterizing the Genetic Basis of Innate Immune Response in ​TLR4-Activated Human Monocytes
Investigators report genetic variants and transcripts that are active only during Toll-like receptor (TLR) signaling and contribute to interindividual differences in immune response. Comparing unstimulated versus ​TLR4-stimulated monocytes reveals 1,471 expression quantitative trait loci that are unique to ​TLR4 stimulation.
[Nat Commun] Abstract

Increase in Activated Treg in TIL in Lung Cancer and In Vitro Depletion of Treg by ADCC Using an Anti-Human CCR4 mAb (KM2760)
Researchers investigated subpopulations of Foxp3⁺ CD4 T cells in PBMCs and TILs in lung cancer. They show that Tregs in healthy donors that express CCR4 could be efficiently eliminated in vitro by co-treatment with anti-human CCR4 mAb and NK cells. [J Thorac Oncol] Abstract

Monocyte-Derived Dendritic Cells Reflect the Immune Functional Status of a Chromophobe Renal Cell Carcinoma Patient: Could it be a General Phenomenon?
Investigators evaluated monocyte-derived dendritic cells (Mo-DCs) in a 34-year-old male who had chromophobe renal cell carcinoma, before and after tumor removal. CD14⁺ monocytes from the patient’s peripheral blood, one week before and three months after partial nephrectomy, were differentiated in vitro into immature and mature Mo-DCs. These were harvested, analyzed by flow cytometry and used as stimulators of allogeneic T cells. [Cancer Immunol Immunother] Abstract

Regulatory/Effector T-Cell Ratio Is Reduced in Coronary Artery Disease
Scientists investigated regulatory T cell (T_reg) and T_reg/effector T-cell ratio in peripheral blood samples from coronary artery disease patients using a new strategy for precise identification of T_reg. [Circ J] Full Article

Activation and Propagation of Tumor-Infiltrating Lymphocytes on Clinical-Grade Designer Artificial Antigen-Presenting Cells for Adoptive Immunotherapy of Melanoma
Researchers optimized a platform to propagate tumor-infiltrating lymphocytes to a clinical scale using K562 cells genetically modified to express costimulatory molecules such as CD86, CD137-ligand, and membrane-bound IL-15 to function as artificial antigen-presenting cells as an alternative to using peripheral blood mononuclear cells feeders. [J Immunother] Abstract | Press Release

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Adaptimmune Announces Interim Results from Pilot Trial of Its Engineered NY-ESO T Cells Targeting Synovial Sarcoma
Adaptimmune Limited announced the release of interim results from a pilot clinical trial 04511 of NY-ESOc259T which uses a patient’s own T cells that have been genetically altered to attack synovial sarcoma cells. [Press release from Adaptimmune Limited discussing research presented at the Connective Tissue Oncology Society’s (CTOS) Annual Meeting, Berlin] Press Release

TxCell to Present on T Cellular Therapy for Autoimmune Diseases
TxCell SA announced that it will present on T cellular therapy for autoimmune diseases. The presentation will be entitled “T Cellular Therapy for Autoimmune Diseases: from Product Development to Market Access.” [Press release from TxCell SA discussing research to be presented at the 7^th National Bio-Therapy Conference 2014, Shanghai] Press Release

Advaxis Provides Clinical Update for Phase I/II Trial of ADXS-HPV Immunotherapy Product Candidate in Anal Cancer
Advaxis, Inc. announced preliminary data from its Phase I/II study of ADXS-HPV in human papillomavirus (HPV) associated anal cancer that indicate a clinical complete response in all seven patients who have completed the treatment regimen. [Advaxis, Inc.] Press Release

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Selecta, JDRF and Sanofi Extend Collaboration to Develop a Synthetic Vaccine Particle Immunotherapy for Type 1 Diabetes
Selecta Biosciences, Inc. and JDRF announced that they have extended their joint research collaboration and attracted Sanofi as a partner in support of their program to develop a synthetic vaccine particle immunotherapy with the long-term goal to treat and potentially prevent the underlying cause of type 1 diabetes. [Selecta Biosciences, Inc.] Press Release

NewLink Genetics Announces Exclusive Worldwide Licensing Agreement for Development of NLG919, an IDO Inhibitor in Phase I, and Research Collaboration for the Discovery of Next Generation IDO/TDO Inhibitors
NewLink Genetics Corporation announced that they have entered into an exclusive worldwide license agreement with Genentech for the development of NLG919, NewLink’s IDO pathway inhibitor. The parties also entered into a research collaboration for the discovery of next generation IDO/TDO compounds. [NewLink Genetics Corporation] Press Release

AgonOx’s OX40 Platform Being Utilized in MedImmune’s Phase I OX40 Agonist Study
AgonOx announced that its OX40 platform is being utilized in MedImmune’s Phase I trial of its humanized OX40 agonist, MEDI6383. OX40 agonists are under clinical development to determine their anti-tumor effect, as they may enhance T-cell stimulation and promote the immune system’s potential to kill tumor cells. [AgonOx] Press Release

Compugen Achieves Second Preclinical Milestone in Cancer Immunotherapy Collaboration with Bayer
Compugen Ltd. disclosed that it has achieved a second milestone in its cancer immunotherapy collaboration it entered last year with Bayer HealthCare. The collaboration provides for the research, development, and commercialization of antibody-based cancer therapeutics against two novel Compugen-discovered immune checkpoint regulators. [Compugen Ltd.] Press Release

Kineta Announces the Opening of the First Psoriasis Clinical Trial Using Novel ShK-186
Kineta, Inc. announced that the company has opened a Phase IB proof-of-concept clinical trial for psoriasis using its drug candidate, ShK-186. ShK-186 is a novel, immune-sparing therapeutic in development for a variety of autoimmune diseases. [Kineta, Inc.] Press Release

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