Volume 3.19 | May 19

Human Immunology News 3.19 May 19, 2015
Human Immunology News
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TOP STORY
How the Tumor Microenvironment Contributes to Drug-Resistant Neuroblastoma
Scientists found that specific microRNAs were exchanged (via exosome “envelopes”) between tumors and tumor-associated macrophages (TAMs), and discovered the process by which cancer cells release these envelopes and TAMs receive them. [Press release from Children’s Hospital Los Angeles discussing online prepublication in Journal of the National Cancer Institute] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Functional Inflammatory Profiles Distinguish Myelin-Reactive T Cells from Patients with Multiple Sclerosis
A total of 13,324 T cell libraries generated from blood of 23 patients and 22 healthy controls were interrogated for reactivity to myelin antigens. Libraries derived from CCR6+ myelin-reactive T cells from patients with multiple sclerosis exhibited significantly enhanced production of interferon-γ, interleukin-17, and granulocyte-macrophage colony-stimulating factor compared to healthy controls. [Sci Transl Med] Abstract | Press Release

Anti-CD20/CD3 T Cell–Dependent Bispecific Antibody for the Treatment of B Cell Malignancies
The authors describe a B cell–targeting anti-CD20/CD3 T cell–dependent bispecific antibody (CD20-TDB), which is a full-length, humanized immunoglobulin G1 molecule with near-native antibody architecture constructed using “knobs-into-holes” technology. CD20-TDB is highly active in killing CD20-expressing B cells, including primary patient leukemia and lymphoma cells both in vitro and in vivo. [Sci Transl Med] Abstract

In Autoimmune Hepatitis Type 1 or the Autoimmune Hepatitis-Sclerosing Cholangitis Variant Defective Regulatory T-Cell Responsiveness to IL-2 Results in Low IL-10 Production and Impaired Suppression
Researchers re-examined phenotypic and functional properties of regulatory T-cell (T-reg) by adopting a more refined definition of these cells that also includes negativity or low level of expression of CD127. They studied 43 autoimmune liver disease patients and 22 healthy subjects and found that CD4+CD25+CD127 T-regs were decreased in the former. [Hepatology] Abstract

Inducible Caspase-9 Suicide Gene Controls Adverse Effects from Alloreplete T Cells after Haploidentical Stem Cell Transplantation
To test the feasibility of a single T-cell manipulation to eliminate alloreactivity while sparing antiviral and antitumor T cells, investigators infused 12 haploidentical hematopoietic stem cell transplant patients with increasing numbers of alloreplete haploidentical T cells expressing the inducible caspase 9 suicide gene (iC9-T cells). They determined whether the iC9-T cells produced immune reconstitution and if any resultant GvHD could be controlled by administration of a chemical inducer of dimerization. [Blood] Abstract | Press Release

Lentivirus-Induced ‘Smart’ Dendritic Cells: Pharmacodynamics and GMP-Compliant Production for Immunotherapy against TRP2 Positive Melanoma
Dendritic cells (DC) generated with monocytes from five advanced melanoma patients were tested in autologous DC:T cell stimulation assays, validating the activation of functional TRP2-specific cytotoxic T lymphocytes for all patients. [Gene Ther] Abstract

Higher Frequency of Regulatory T Cells in Granulocyte Colony-Stimulating Factor (G-CSF)-Primed Bone Marrow Grafts Compared with G-CSF-Primed Peripheral Blood Grafts
Scientists compared the contents of regulatory T cells and effector T cells in G-CSF-primed bone marrow grafts and peripheral blood grafts. [J Transl Med] Abstract | Full Article

Peripheral Dendritic Cells and CD4+CD25+Foxp3+ Regulatory T Cells in the First Trimester of Normal Pregnancy and in Women with Recurrent Miscarriage
Investigators compared the population of circulating dendritic cells and CD4+CD25+Foxp3+ regulatory T cells in the first trimester of a normal pregnancy and in women with recurrent miscarriage and an attempt to determine the relationship between these cells and the role they may play in human reproductive failures. [PLoS One] Full Article

Differential Regulation and Function of Tumor-Infiltrating T Cells in Different Stages of Breast Cancer Patients
Scientists examined the functions and regulations of CD8+ T cells and CD4+CD25+FoxP3+ T cells from resected tumors from 12 stage I, 24 stage II, and 20 stage III untreated breast cancer patients. They found that tumor-infiltrating CD8+ T cells from stage III patients were more refractory to T cell receptor stimulation than those from stage I and stage II patients in terms of interferon gamma production and proliferation. [Tumor Biol] Abstract

Aberrant Expression of Regulatory Cytokine IL-35 in Patients with Systemic Lupus Erythematosus
Researchers characterized an IL-35-mediated regulatory role in patients with systemic lupus erythematosus (SLE). Their findings indicated that high level of plasma IL-35 in active SLE patients expressed with low level of IL-35 receptor on CD4+ helper cells. [Lupus] Abstract

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REVIEWS
Classifying Cancers Based on T-Cell Infiltration and PD-L1
It has been proposed that four different types of tumor microenvironment exist based on the presence or absence of tumor-infiltrating lymphocytes and programmed death-ligand 1 (PD-L1) expression. Investigators review this stratification and the latest in a series of results that shed light on new approaches for rationally designing ideal combination cancer therapies based on tumor immunology. [Cancer Res] Abstract

Epigenetic Dynamics during CD4+ T Cells Lineage Commitment
The authors review the contribution of epigenetic mechanisms to transcriptional control during CD4 T cell differentiation and the ways in which these mechanisms interact with key transcription factors to ensure proper maturation and maintenance of cell identity. [Int J Biochem Cell Biol] Abstract

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SCIENCE NEWS
Genentech’s Investigational Immunotherapy MPDL3280A Doubled the Likelihood of Survival Compared with Chemotherapy in People with a Specific Type of Lung Cancer
Genentech announced interim results from a global, randomized Phase II study in people with previously treated non-small cell lung cancer (NSCLC). The study showed the investigational cancer immunotherapy MPDL3280A doubled the likelihood of survival in people whose cancer expressed the highest levels of PD-L1 (programmed death ligand-1) compared with docetaxel chemotherapy. [Press release from Genentech, Inc. discussing research to be presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

New Troops in the Fight against Cancer
Pembrolizumab has shown anti-tumor activity in numerous advanced malignancies, including melanoma and non-small cell lung cancer. This clinical trial in particular focused on the activity of pembrolizumab in tumors with high PD-L1 expression, which may predict response to pembrolizumab. [Press release from Rutgers Cancer Institute of New Jersey discussing research to be presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Agenus Announces Oral Presentation Highlighting Improved Survival with Prophage Immunotherapy in Brain Cancer Compared to Historical Controls
Agenus Inc. announced that data on continuing survival from a Phase II study of its Prophage vaccine in glioblastoma multiforme has been selected for an oral presentation. [Press release from Agenus Inc. discussing research to be presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Generex Provides Data Update from AE37 Phase II Breast Cancer Trial One Year Post Completion of Enrollment
Generex Biotechnology Corporation announced that updated data from the on-going Phase II clinical trial of the AE37 breast cancer vaccine under development at the company’s wholly-owned subsidiary, Antigen Express, Inc., will be presented. [Press release from Generex Biotechnology Corporation discussing research to be presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Argos Therapeutics Provides Update on Enrollment Progress for Ongoing Pivotal Phase III ADAPT Clinical Trial
Argos Therapeutics Inc. announced that more than 1,000 tumor samples have been collected and approximately 400 eligible patients have been randomized to the company’s ongoing, pivotal Phase III ADAPT clinical trial of AGS-003 for the treatment of metastatic renal cell carcinoma. [Press release from Argos Therapeutics Inc. discussing research to be presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Celsion Corporation Announces GEN-1 Immunotherapy Phase Ib Results in Ovarian Cancer Presentation
Celsion Corporation announced that results from its Phase Ib trial for GEN-1 in platinum-resistant ovarian cancer will be presented in poster session. GEN-1 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. [Press release from Celsion Corporation discussing research to be presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

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INDUSTRY NEWS
Lilly and Sanford-Burnham Announce Collaboration to Investigate Immunological Therapies
Eli Lilly and Company and Sanford-Burnham Medical Research Institute will investigate potential therapeutics using biotechnology approaches in targeting multiple immune checkpoint modulators for the treatment of immunological diseases such as lupus, Sjögren’s syndrome, inflammatory bowel disease and other autoimmune disorders. [Eli Lilly and Company] Press Release

Selecta and Généthon Collaborate to Create Next Generation Gene Therapies Using Selecta’s Synthetic Vaccine Particle Platform
Selecta Biosciences, Inc. and Généthon announced an ongoing research collaboration with the goal of enabling repeat dosing for gene therapies. Based on preliminary results, the companies have identified three applications that might benefit from combining Généthon’s expertise in the development of gene therapy vectors and Selecta’s synthetic vaccine particle platform to prevent undesired immune responses. [Selecta Biosciences, Inc.] Press Release

Advaxis and Sorrento Form Collaboration to Evaluate Combinations of Advaxis’s Lm-LLO Immunotherapy Technology and Sorrento’s Immunomodulatory Antibodies
Advaxis, Inc. has entered into a non-exclusive research and clinical trial collaboration agreement with Sorrento Therapeutics, Inc. to evaluate combinations of Advaxis’s Lm-LLO cancer immunotherapy technology platform, including ADXS-HPV, ADXS-PSA and ADXS-HER2, with Sorrento’s fully human antibodies targeting immune checkpoints, including GITR, OX40, LAG-3 and TIM-3. [Advaxis, Inc.] Press Release

BioNTech and Genmab Sign Co-Development and Commercialization Agreement
BioNTech AG announced that it has signed an agreement with Genmab A/S to jointly research, develop and commercialize multiple bispecific antibodies for cancer immunotherapy using proprietary technologies from both companies: BioNTech’s proprietary immunomodulatory antibodies and Genmab’s DuoBody® technology platform. [BioNTech AG] Press Release

NCCN Receives $2 Million Funding Commitment from ImmunoGen, Inc. to Study Mirvetuximab Soravtansine for Folate Receptor Alpha-Positive Cancers
The National Comprehensive Cancer Network® (NCCN®) Oncology Research Program has been awarded a $2 million grant from ImmunoGen, Inc. to support the advancement of scientific knowledge related to mirvetuximab soravtansine, a potential new treatment for ovarian and other folate receptor alpha-positive cancers. [National Comprehensive Cancer Network®] Press Release

Texas A&M Researchers Looking to Microbiota to Advance Personalized Medicine
The host-microbiota connection serves as the driving force for a multi-institutional team of researchers led by Robert Alaniz, Ph.D., assistant professor at the Texas A&M College of Medicine. Their work, which recently received a $2 million grant from the National Institutes of Health, focuses on understanding how the microbiota regulate T-cells, which are meant to help protect your body. [Texas A&M College of Medicine] Press Release

Sorrento Establishes TNK Therapeutics Subsidiary with Focus on Cellular Immunotherapies
Sorrento Therapeutics, Inc. announced that it has formed a wholly-owned subsidiary, TNK Therapeutics, Inc. This subsidiary will focus on developing CAR.TNKs (chimeric antigen receptor tumor-attacking neukoplast®) as well as other complementary cellular and immunotherapies targeting both solid tumors and hematological malignancies. [Sorrento Therapeutics, Inc.] Press Release
 
POLICY NEWS
National Institutes of Health (United States)

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)
 
EVENTS
NEW International Congress of Mucosal Immunology (ICMI) 2015
July 14-18, 2015
Berlin, Germany

Visit our events page to see a complete list of events in the human immunology community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Fellow – Immune Tolerance (Stanford University)

NEW Research Scientist – Immunology (Gilead Sciences)

NEW PhD Position – Microbial Immunology (Hans Knöll Institute)

Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Process Facilitator (Opexa Therapeutics)

Scientist – Immunology Discovery (Genentech, Inc.)

Scientist – Clinical Immunology (Amgen, Inc.)

Postdoctoral Position – Immunology (University of California, San Francisco)

Postdoctoral Position – Immunology (Institut Curie)


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