Immune Regulation News Volume 6.42 | Nov 7 2014

Adiposity Induces Lethal Cytokine Storm after Systemic Administration of Stimulatory Immunotherapy Regimens in Aged Mice
Researchers determined the effects of adiposity on systemic immunotherapy tolerance in aged compared with young obese mice. Young obese mice exhibited greater ratios of M1/M2 macrophages within the peritoneal and visceral adipose tissues and higher percentages of TNF⁺ macrophages in response to αCD40/IL-2 as compared with young lean mice. [J Exp Med] Abstract | Press Release

Interleukin 10 Modulation of Pathogenic Th17 Cells during Fatal Alphavirus Encephalomyelitis
To determine the reason for accelerated disease in the absence of IL-10, immune responses in the CNS of IL-10^−/− and wild-type (WT) mice were compared. There were no differences in the amounts of brain inflammation or peak virus replication; however, IL-10^−/− animals had accelerated and increased infiltration of CD4⁺IL-17A⁺ and CD4⁺IL-17A⁺IFNγ⁺ cells compared with WT animals. [Proc Natl Acad Sci USA] Abstract

Signaling Pathways Activated by a Protease Allergen in Basophils
Researchers characterized the cellular response activated by papain in basophils. They found that papain-induced IL-4 production requires calcium flux and activation of PI3K and nuclear factor of activated T cells. [Proc Natl Acad Sci USA] Abstract

Granzyme A Produces Bioactive IL-1β through a Nonapoptotic Inflammasome-Independent Pathway
Investigators show that the bacterial Pasteurella multocida toxin (PMT) triggers Il1b gene transcription in macrophages independently of Toll-like receptor signaling through RhoA/Rho-kinase-mediated NF-κΒ activation. Furthermore, PMT mediates signal transducer and activator of transcription protein-controlled granzyme A expression in macrophages. [Cell Rep] Full Article | Graphical Abstract

Structure and Cancer Immunotherapy of the B7 Family Member B7x
Scientists developed an in vivo system to screen therapeutic monoclonal antibodies against B7x and found that the clone 1H3 significantly inhibited growth of B7x-expressing tumors in vivo via multiple mechanisms. Furthermore, the surviving mice given 1H3 treatment were resistant to tumor rechallenge. [Cell Rep]
Full Article | Graphical Abstract

Non-Viral Immune Electrogene Therapy Induces Potent Antitumor Responses and Has a Curative Effect in Murine Colon Adenocarcinoma and Melanoma Cancer Models
Antitumor efficacy of electroporated proof-of-concept enhanced expression vector, coding for granulocyte-macrophage colony-stimulating factor and the B7-1 costimulatory immune molecule in growing solid tumors, was investigated and compared with a standard plasmid. [Gene Ther] Full Article

EBAG9 Modulates Host Immune Defense against Tumor Formation and Metastasis by Regulating Cytotoxic Activity of T Lymphocytes
Scientists investigated the role of estrogen receptor-binding fragment-associated antigen 9 (EBAG9) in host defense against implanted tumors in Ebag9-knockout (Ebag9KO) mice. The infiltration of CD8⁺, CD3⁺ and CD4⁺ T cells into the generated tumors was enhanced in Ebag9KO mice compared with controls. [Oncogenesis] Full Article

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Lessons from Rodent Models in Celiac Disease
The authors review how approaches in rodents have provided insight into celiac disease pathophysiology and also highlight the difficulties met to fully recapitulate the human disease. [Mucosal Immunol] Abstract

Autophagy and Hematopoietic Stem Cell Transplantation
The authors cover established and implicated roles of autophagy in hematopoietic stem cell transplantation, suggesting this pathway as an important therapeutic target for improving transplant outcomes. [Immunol Cell Biol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Advaxis to Present Survival Data of Lm-LLO Cancer Immunotherapies in Recurrent Cervical Cancer and Canine Osteosarcoma
Advaxis, Inc. announced the abstracts of three preclinical and clinical studies highlighting the survival outcomes and anti-tumor effects of its proprietary Lm-LLO cancer immunotherapy technology. [Press release from Advaxis, Inc. discussing research to be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, National Harbor] Press Release

Five Prime Therapeutics Announces Presentation
Five Prime Therapeutics, Inc. announced that it will present a poster describing the use of the company’s protein screening platform to identify unique cancer immunotherapy targets. [Press release from Five Prime Therapeutics, Inc. discussing research to be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, National Harbor] Press Release

Galena Biopharma Presents GALE-301 (Folate Binding Protein Immunotherapy) Phase IIa Clinical Trial Data
Galena Biopharma, Inc. announced that data from the company’s Phase I/IIa trial of GALE-301, a folate binding protein-derived immunotherapy, will be presented. [Press release from Galena Biopharma, Inc. discussing research to be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, National Harbor] Press Release

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FDA Issues IND Number for Regen BioPharma’s dCellVax Therapeutic Application, a Proposed Treatment for Breast Cancer
Regen BioPharma, Inc. announced issuance of IND (Investigational New Drug Application) number 16200 from the FDA for a proposed Phase I/II clinical trial assessing safety with signals of efficacy of the dCellVax gene silenced dendritic cell immunotherapy for treating breast cancer. [Regen BioPharma, Inc. (Marketwire L.P.)] Press Release

MedImmune Strengthens Immuno-Oncology Capabilities with Acquisition of Definiens
AstraZeneca announced that MedImmune has entered into an agreement to acquire Definiens, a privately-held company that has pioneered a world-leading imaging and data analysis technology, known as Tissue Phenomics™, which dramatically improves the identification of biomarkers in tumor tissue. [AstraZeneca] Press Release

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

Visit our events page to see a complete list of events in the immune regulation community.

NEW Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant)

NEW Postdoctoral Research Fellow – Immune and Pathogenic Mechanisms during Alphavirus Infection (Singapore Immunology Network A*STAR)

Postdoctoral Research Fellow – Mucosal Immune System in Chronic and Infectious Disease (Griffith Health Institute)

Postdoctoral Research Fellow – Immune Responses to HSV (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Genetic and Epigenetic Regulatory Networks in Protective Immune Responses (Washington University School of Medicine)

Postdoctoral Fellowship – Development of Autoimmunity and Cancer (Mount Sinai Medical Center)

PhD Studentship – Cancer Immunology (Cardiff University)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

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