Human Immunology News 3.04 February 3, 2015
Protein-Based Therapy Shows Promise against Resistant Leukemia
Resistance of leukemia cells to contemporary chemotherapy is one of the most formidable obstacles to treating acute lymphoblastic leukemia, the most common form of childhood cancer. Now researchers have designed and developed a new protein-based therapy they believe will prove highly effective against drug-resistant leukemia cells. [Press release from Children's Hospital Los Angeles discussing online publication in The Journal of Clinical Investigation] Press Release | Full Article
Tracking Donor-Reactive T Cells: Evidence for Clonal Deletion in Tolerant Kidney Transplant Patients
Scientists established an assay to identify donor-reactive T cells and test the role of deletion in tolerance after combined kidney and bone marrow transplantation. Using high-throughput sequencing of the T cell receptor B chain CDR3 region, they define a fingerprint of the donor-reactive T cell repertoire before transplantation and track those clones after transplant. [Sci Transl Med] Abstract
Mast Cells Form Antibody-Dependent Degranulatory Synapse for Dedicated Secretion and Defense
Investigators show that interaction of mast cells with antibody-targeted cells induces the polarized exocytosis of their granules resulting in a sustained exposure of effector enzymes, such as tryptase and ​chymase, at the cell-cell contact site. This previously unidentified mast cell effector mechanism is triggered by both IgE- and IgG-targeted cells. [Nat Commun] Abstract
Effector Vγ9Vδ2 T Cells Dominate the Human Fetal γδ T-Cell Repertoire
Researchers show that, rather than requiring postnatal microbial exposure, T cells expressing the T-cell receptor containing the γ-chain variable region 9 and the δ-chain variable region 2 (Vγ9Vδ2 T cells) are the predominant blood subset in the second-trimester fetus, whereas Vδ1+ and Vδ3+ γδ T cells are present only at low frequencies at this gestational time. [Proc Natl Acad Sci USA] Abstract
Nonapoptotic and Extracellular Activity of Granzyme B Mediates Resistance to Regulatory T Cell (Treg) Suppression by HLA-DR–CD25hiCD127lo Tregs in Multiple Sclerosis and in Response to IL-6
Scientists show that memory CD4+CD127loFOXP3+ Treg subsets do not express granzyme B (GzmB), whereas activated, nonregulatory CD4 T cells isolated from patients with multiple sclerosis express higher levels of GzmB than do cells from healthy donors. [J Immunol] Abstract
Soluble Tim-3 Is Shed from CD8+ T Cells by the Sheddase ADAM10, Is Increased in Plasma during Untreated HIV Infection, and Correlates with HIV Disease Progression
Investigators show that T cell immunoglobulin mucin domain-3 (Tim-3) is shed from the surface of responding CD8+ T cells by the matrix metalloproteinase, ADAM10, producing a soluble form of the co-inhibitory receptor. Despite previous reports in the mouse model, no alternatively spliced, soluble form of Tim-3 was observed in humans. [J Virol] Abstract
Viral Restriction Factor Tetherin Prevents Leucine-Rich Pentatricopeptide Repeat Containing Protein (LRPPRC) from Association with Beclin 1 and B-Cell CLL/Lymphoma 2 (Bcl-2) and Enhances Autophagy and Mitophagy
Tetherin has been characterized as a key factor that restricts viral particles such as HIV and hepatitis C virus on plasma membranes, acts as a ligand of immunoglobulin-like transcript 7 receptor in tumor cells, and suppresses antiviral innate immune responses mediated by human plasmacytoid dendritic cells. Scientists show that tetherin not only serves as a substrate of autophagy but itself regulates the initiation of autophagy. [J Biol Chem] Abstract | Full Article
Aspartate-β-Hydroxylase Induces Epitope-Specific T Cell Responses in Hepatocellular Carcinoma
Investigators observed that aspartate-β-hydroxylase protein and related peptides were highly immunogenic in patients with hepatocellular carcinoma and produce the type of cellular immune responses required for generation of anti-tumor activity. [Vaccine] Abstract
Heterogeneous Expansion of CD4+ Tumor-Infiltrating T-Lymphocytes in Clear Cell Renal Cell Carcinomas
Researchers utilized deep sequencing of T-cell receptor beta chains, which serve as a unique identifier for each T clonotype, to characterize the CD4+/CD8+ tumor-infiltrating T-lymphocytes repertoire in clear cell renal cell carcinoma patients, assess the diversity and clonality of infiltrated T-cells in distinct tissues from patients and depict the clonal expansion events that occur in anti-tumor immune responses. [Biochem Biophys Res Commun] Abstract
Adoptive T-Cell Therapy of Prostate Cancer Targeting the Cancer Stem Cell Antigen EpCAM
An EpCAM-specific chimeric antigen receptor (CAR) was constructed to transduce human peripheral blood lymphocytes (PBLs) and thereby enable them to target the cancer stem cell marker EpCAM. Scientists demonstrate that CAR-expressing PBLs can kill a highly metastatic clone of PC3 tumor cells in vitro and in vivo. [BMC Immunol] Abstract | Full Article
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Alloantibodies to Therapeutic Factor VIII in Hemophilia A: The Role of Von Willebrand Factor in Regulating Factor VIII Immunogenicity
The rising incidence of neutralizing antibodies against therapeutic factor VIII (FVIII) prompted the conduct of studies to answer the question as to whether this rise is related to the introduction of recombinant FVIII products. The authors summarize current opinions and results of non-clinical and clinical studies on the immunogenic potential of recombinant compared to plasma-derived FVIII concentrates. [Haematologica]
Dendritic Cells and Innate Immunity in Kidney Transplantation
The review summarizes emerging concepts related to the roles of dendritic cells (DCs) and innate immunity in organ transplant rejection. It highlights the primary role that recipient, rather than donor, DCs have in rejection and reviews their origin and function in the transplanted kidney. [Kidney Int] Abstract
Manchester to Lead Project for Better Lupus Treatment
The University of Manchester is to lead a new £5.1 million consortium of universities and industry partners in a project aimed at eliminating the 'trial and error' approach to the treatment of lupus. [The University of Manchester] Press Release
FDA Grants Breakthrough Therapy Designation for Genentech's Investigational Cancer Immunotherapy MPDL3280A (Anti-PDL1) in Non-Small Cell Lung Cancer
Genentech announced that it has received a second Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for its investigational cancer immunotherapy MPDL3280A. [Genentech Inc.]
MMRGlobal Biotech Assets in Play as Company Is Awarded Second U.S. Cancer Fighting Patent
MMRGlobal, Inc. announced that U.S. Patent No. 8,945,550 will issue, providing the second U.S. patent, in addition to patents in Australia, Mexico and South Korea, for the company's anti-CD20 monoclonal antibody technology. [MMRGlobal, Inc.] Press Release
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NEW 24th Annual Canadian Association for HIV Research (CAHR) Conference 2015
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Research Scientist – Cancer Immunotherapy (iTeos Therapeutics)