Human Immunology News Volume 5.27 | Jul 11 2017

TOP STORY

An Immunogenic Personal Neoantigen Vaccine for Patients with Melanoma

Investigators hypothesized that vaccination with neoantigens can both expand pre-existing neoantigen-specific T-cell populations and induce a broader repertoire of new T-cell specificities in cancer patients, tipping the intra-tumoral balance in favor of enhanced tumor control. They demonstrated the feasibility, safety, and immunogenicity of a vaccine that targets up to 20 predicted personal tumor neoantigens. [Nature] Abstract | Press Release

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Stabilization of the c-Myc Protein by CAMKIIγ Promotes T Cell Lymphoma

Ca²⁺/calmodulin-dependent protein kinase II γ (CAMKIIγ) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). CAMKIIγ was shown to be essential for tumor maintenance. Inhibition of CAMKIIγ with a specific inhibitor destabilized c-Myc and reduced tumor burden. High CAMKIIγ levels in patient T cell lymphoma specimens correlate with increased c-Myc and pS62-c-Myc levels. [Cancer Cell] Abstract | Graphical Abstract

Mutations in 5-Methylcytosine Oxidase TET2 and RhoA Cooperatively Disrupt T Cell Homeostasis

The authors demonstrated that TET2 loss and RhoA^G17V expression in mature murine T cells cooperatively cause abnormal CD4⁺ T cell proliferation and differentiation by perturbing FoxO1 gene expression, phosphorylation, and subcellular localization, an abnormality that is also detected in human primary angioimmunoblastic T cell lymphoma tumor samples. [J Clin Invest] Full Article

The Calreticulin (CALR) Exon 9 Mutations Are Promising Targets for Cancer Immune Therapy

Scientists describe how CALR-mutant (CALRmut)-specific T-cells are able to specifically recognize CALRmut cells. They established a T-cell culture specific for a CALRmut epitope. These specific T-cells were able to recognize several epitopes in the CALRmut C-terminus. They established a CALRmut specific CD4⁺ T-cell clone by limiting dilution. [Leukemia] Abstract

Increased Expression of Programmed Cell Death Protein 1 on NK Cells Inhibits NK-Cell-Mediated Anti-Tumor Function and Indicates Poor Prognosis in Digestive Cancers

Researchers showed that programmed cell death protein 1, a well-known immune checkpoint of T cells, was highly expressed on peripheral and tumor-infiltrating natural killer (NK) cells from patients with digestive cancers including esophageal, liver, colorectal, gastric and biliary cancer. [Oncogene] Abstract

Lipodystrophy and Obesity Are Associated with Decreased Numbers of T Cells with Regulatory Function and Pro-Inflammatory Macrophage Phenotype

Scientists aimed to investigate whether T-cells populations with regulatory function and monocyte-derived macrophages are affected by lipodystrophy and obesity. [Int J Obes (Lond)] Abstract

5T4-Specific Chimeric Antigen Receptor Modification Promotes the Immune Efficacy of Cytokine-Induced Killer Cells against Nasopharyngeal Carcinoma Stem Cell-Like Cells

The authors aimed to identify appropriate tumor-associated antigens predominantly expressed on nasopharyngeal carcinoma (NPC) stem cells and determine their suitability for chimeric antigen receptor-engineered cytokine-induced killer cell therapy against NPC. [Sci Rep] Full Article

Effector T Helper Cell Populations Are Elevated in the Bone Marrow of Rheumatoid Arthritis Patients and Correlate with Disease Severity

Scientists investigated the frequencies of T-helper (Th)22, Th17 and Th1 cells and the levels of related cytokines in subchondral bone marrow in patients with rheumatoid arthritis. [Sci Rep] Full Article

Human Neonatal Thymectomy Induces Altered B-Cell Responses and Auto-Reactivity

An association between T-cell lymphopenia and autoimmunity has long been proposed, but it remains to be elucidated whether T-cell lymphopenia affects B-cell responses to auto-antigens. Human neonatal thymectomy results in a decrease in T-cell numbers and investigators used this model to study the development of auto-reactivity. [Eur J Immunol] Abstract

Significant Augmentation of Regulatory T Cell Numbers Occurs during the Early Neonatal Period

Researchers examined the number and phenotype of regulatory T cells (Tregs) during the neonatal period in 49 newborn babies. Tregs were characterized by flow cytometry using cord blood and peripheral blood from the early and late neonatal periods. CD4⁺ Foxp3⁺ T cells were classified into resting Tregs (CD45RA⁺ Foxp3^low), activated Tregs (CD45RA^– Foxp3^high), and newly activated T cells (CD45RA^– Foxp3^low). [Clin Exp Immunol] Abstract

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Cytoskeletal Control of B Cell Responses to Antigens

The author discusses recent insights from studies using single-cell imaging and biophysical techniques, which suggest that actin orchestrates B cell receptor signaling at the plasma membrane through effects on protein diffusion and that it regulates antigen discrimination through the biomechanics of immune synapses. [Nat Rev Immunol] Abstract

miRNAs in B Cell Development and Lymphomagenesis

Scientists provide an overview of the current knowledge on the role of miRNAs and their relevant targets in B cell development, B cell activation, and B cell malignant transformation. [Trends Mol Med] Abstract

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Celgene Corporation Enters into Global Strategic Immuno-Oncology Collaboration with BeiGene to Advance PD-1 Inhibitor Program for Solid Tumor Cancers

Celgene Corporation and BeiGene, Ltd. entered into a strategic collaboration to develop and commercialize BeiGene’s investigational anti-programmed cell death protein 1 (PD-1) inhibitor, BGB-A317, for patients with solid tumor cancers in the United States, Europe, Japan and rest of world outside Asia. [Celgene Corporation] Press Release

PDS Biotechnology Corp. Announces Clinical Collaboration with Merck to Evaluate Combination of Versamune^® pds0101 and Keytruda^® for Metastatic Head and Neck Cancer

PDS Biotechnology Corporation has entered a clinical trial collaboration agreement with a subsidiary of Merck to evaluate the combination of PDS’s lead Versamune^®-based immunotherapy, PDS0101, with Merck’s anti-PD-1 therapy, KEYTRUDA^®, in a Phase II clinical trial. The planned clinical trial will evaluate the safety and efficacy of the combination in patients with recurrent or metastatic head and neck cancer and high-risk human papillomavirus-16 infection after failure with platinum-based chemotherapy. [PDS Biotechnology Corporation] Press Release

ViraCyte Awarded $3.75M from NIH and FDA to Advance T Cell Immunotherapies

ViraCyte, LLC. announced that it has been awarded $3.75M from National Institutes of Health (NIH) and the FDA to advance its T cell immunotherapies. [ViraCyte, LLC.] Press Release

BioLineRx Announces Initiation of Phase Ib/II Trial of BL-8040 in Pancreatic Cancer under Immunotherapy Collaboration

BioLineRx Ltd. announced that Genentech has commenced a Phase Ib/II study for BL-8040 in combination with TECENTRIQ^®, Genentech’s anti-PDL1 cancer immunotherapy agent, evaluating the combination in metastatic pancreatic ductal adenocarcinoma. [BioLineRx Ltd.] Press Release

Kadmon Announces Interim Phase II Data of KD025 in Chronic Graft-Versus-Host Disease

Kadmon Holdings, Inc. announced positive interim results from its ongoing Phase II clinical trial evaluating KD025, the company’s Rho-associated coiled-coil kinase 2 inhibitor, in patients with previously treated chronic graft-versus-host disease, a serious complication following allogeneic bone marrow or stem cell transplantation. In a preliminary analysis, KD025 demonstrated a favorable safety and tolerability profile in all patients and an overall response rate of 71%. [Kadmon Holdings, Inc.] Press Release

ViraCyte Completes Phase I Clinical Trial of Viralym-C

ViraCyte, LLC. announced the successful completion of a Phase I clinical trial using Viralym-C, a “ready to administer” T cell immunotherapy product for the treatment of cytomegalovirus infection in hematopoietic stem cell transplant recipients. [ViraCyte, LLC.] Press Release

First in Human Administration of UCART123 in Cellectis’ AML Phase I Clinical Trial at Weill Cornell Medicine, New York-Presbyterian Hospital

Cellectis announced the first administration in the Phase I clinical study in acute myeloid leukemia (AML) for its investigational product UCART123, one of the company’s wholly-controlled TALEN^® gene-edited product candidates. This marks the first allogeneic, “off-the-shelf” gene-edited CAR T-cell product candidate targeting CD123 to be investigated in clinical trials. [Cellectis] Press Release

Encyt Technologies, Inc. Announces a Potential Breakthrough Approach to Enhance Immunotherapy Treatment

Encyt Technologies, Inc. recently filed a series of patents for novel treatments to reverse resistance to immunotherapy using checkpoint inhibitors. [Encyt Technologies, Inc. (PR Newswire Association LLC.)] Press Release

White House’s Dwindling Science Office Leaves Major Research Programs in Limbo

US President Donald Trump has pledged to shrink the federal government, and he seems to be starting with science. Nearly six months after taking office, Trump has not chosen a science adviser, and the White House’s Office of Science and Technology Policy has dwindled from around 130 staff members under former president Barack Obama to 35. [Nature News] Editorial

French Scientist Fined for Failure to Disclose Industry Ties

In an unprecedented court case in Paris, an eminent French lung specialist has been fined €50,000 and given a six-month suspended jail sentence because he didn’t disclose his ties to the oil industry during a Senate air-pollution inquiry. [Nature News] Editorial

NEW American College of Allergy, Asthma, & Immunology (ACAAI)
October 26-30, 2017
Boston, Massachusetts, United States

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NEW Postdoctoral Research Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Fellow – Neuroimmunology (Duke University)

Postdoctoral Fellow – Immunology (Oxford University)

Postdoctoral Fellow – Cell Biology and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden)

Postdoctoral Position in Mucosal Immunology (Columbia University)

Full Professorship – Immunology (The Max Delbrück Center for Molecular Medicine)

Postdoctoral Fellow – Inflammatory Bowel Disease (Harvard Medical School)

Postdoctoral Research Scientist – Immunogenomics (University of Oxford)

Postdoctoral Research Fellow – Innate Immunity (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Innate and Adaptive Immunity (Stanford University)

Assistant Associate – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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