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Translational immunology

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https://www.readbyqxmd.com/read/28725428/highlights-of-the-31st-annual-meeting-of-the-society-for-immunotherapy-of-cancer-sitc-2016
#1
REVIEW
James L Gulley, Elizabeth A Repasky, Laura S Wood, Lisa H Butterfield
Therapeutic efforts to engage the immune system against cancer have yielded exciting breakthroughs and a growing list of approved immune-based agents across a variety of disease states. Despite the early successes and durable responses associated with treatments such as immune checkpoint inhibition, there is still progress to be made in the field of cancer immunotherapy. The 31st annual meeting of the Society for Immunotherapy of Cancer (SITC 2016), which took place November 11-13, 2016 in National Harbor, Maryland, showcased the latest advancements in basic, translational, and clinical research focused on cancer immunology and immunotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28722289/concise-review-a-safety-assessment-of-adipose-derived-cell-therapy-in-clinical-trials-a-systematic-review-of-reported-adverse-events
#2
REVIEW
Navid Mohamadpour Toyserkani, Mads Gustaf Jørgensen, Siavosh Tabatabaeifar, Charlotte Harken Jensen, Søren Paludan Sheikh, Jens Ahm Sørensen
The popularity of adipose-derived cell therapy has increased over the last decade, and the number of studies published annually is growing. However, concerns regarding safety in the setting of previous malignancy or the use of allogeneic cells have been raised. We therefore aimed to systematically review all clinical studies using adipose-derived cell therapy to identify reported adverse events with a special focus on risk of thromboembolic, immunological and oncological safety concerns. Our systematic search resulted in 70 included studies involving more than 1,400 patients that were treated with adipose-derived cell therapy...
July 19, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28720686/oncolytic-virus-induced-cell-death-and-immunity-a-match-made-in-heaven
#3
REVIEW
Jolien De Munck, Alex Binks, Iain A McNeish, Joeri L Aerts
Our understanding of the mechanisms responsible for cancer development has increased enormously over the last decades. However, for many cancers, this has not been translated into a significant improvement in overall survival, and overall mortality remains high. Treatment for many malignancies remains based on surgery, chemotherapy, and radiotherapy. Significant progress has been made toward the development of more specific, more potent, and less invasive treatment modalities, but such targeted therapies remain the exception for most cancers...
July 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28720430/oncogenic-pathways-that-affect-antitumor-immune-response-and-immune-checkpoint-blockade-therapy
#4
REVIEW
Xianda Zhao, Subbaya Subramanian
Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitumor immune response. Such oncogenic signaling, in turn, activates many inhibitory factors, including expression of immune checkpoint genes-allowing active infiltration of immunosuppressive cells into the tumor environment and inducing resistance against T-cell killing...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28716068/highlights-of-the-31st-annual-meeting-of-the-society-for-immunotherapy-of-cancer-sitc-2016
#5
REVIEW
James L Gulley, Elizabeth A Repasky, Laura S Wood, Lisa H Butterfield
Therapeutic efforts to engage the immune system against cancer have yielded exciting breakthroughs and a growing list of approved immune-based agents across a variety of disease states. Despite the early successes and durable responses associated with treatments such as immune checkpoint inhibition, there is still progress to be made in the field of cancer immunotherapy. The 31st annual meeting of the Society for Immunotherapy of Cancer (SITC 2016), which took place November 11-13, 2016 in National Harbor, Maryland, showcased the latest advancements in basic, translational, and clinical research focused on cancer immunology and immunotherapy...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28704211/how-to-emerge-from-the-conservatism-in-clinical-research-methodology
#6
Nuria Kotecki, Nicolas Penel, Ahmad Awada
PURPOSE OF REVIEW: Despite recent changes in clinical research methodology, many challenges remain in drug development methodology. RECENT FINDINGS: Advances in molecular biology and cancer treatments have changed the clinical research landscape. Thus, we moved from empirical clinical oncology to molecular and immunological therapeutic approaches. Along with this move, adapted dose-limiting toxicities definitions, endpoints, and dose escalation methods have been proposed...
July 12, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28696328/of-mice-dirty-mice-and-men-using-mice-to-understand-human-immunology
#7
REVIEW
David Masopust, Christine P Sivula, Stephen C Jameson
Mouse models have enabled breakthroughs in our understanding of the immune system, but it has become increasingly popular to emphasize their shortcomings when translating observations to humans. This review provides a brief summary of mouse natural history, husbandry, and the pros and cons of pursuing basic research in mice versus humans. Opportunities are discussed for extending the predictive translational value of mouse research, with an emphasis on exploitation of a "dirty" mouse model that better mimics the diverse infectious history that is typical of most humans...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28683176/possible-cleavage-sites-of-glutelin-partial-degradation-confirmed-by-immunological-analysis-in-globulin-less-mutants-of-rice-oryza-sativa-l
#8
Nadar Khan, Satoru Yamaguchi, Tomoyuki Katsube-Tanaka
Proteolytic cleavage or partial degradation of proteins is one of the important post-translational modifications for various biological processes, but it is difficult to analyze. Previously, we demonstrated that some subunits of the major rice (Oryza sativa L.) seed storage protein glutelin are partially degraded to produce newly identified polypeptides X1-X5 in mutants in which another major seed storage protein globulin is absent. In this study, the new polypeptides X3 and X4/X5 were immunologically confirmed to be derived from GluA3 and GluA1/GluA2 subunits, respectively...
July 6, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28681110/recent-advances-in-cmv-tropism-latency-and-diagnosis-during-aging
#9
Sean X Leng, Jeremy Kamil, John G Purdy, Niels A Lemmermann, Matthias J Reddehase, Felicia D Goodrum
Human cytomegalovirus (CMV) is one of the largest viruses known to cause human diseases. Chronic CMV infection, as defined by anti-CMV IgG serology, increases with age and is highly prevalent in older adults. It has complex biology with significant immunologic and health consequences. This article aims to summarize research findings presented at the 6th International Workshop on CMV and Immunosenescence that relate to advances in the areas of CMV tropism, latency, CMV manipulation of cell metabolism, and T cell memory inflation, as well as novel diagnostic evaluation and translational research of chronic CMV infection in older adults...
June 2017: GeroScience
https://www.readbyqxmd.com/read/28638807/translational-rodent-models-for-research-on-parasitic-protozoa-a-review-of-confounders-and-possibilities
#10
REVIEW
Totta Ehret, Francesca Torelli, Christian Klotz, Amy B Pedersen, Frank Seeber
Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28620376/the-n-glycosylation-of-mouse-immunoglobulin-g-igg-fragment-crystallizable-differs-between-igg-subclasses-and-strains
#11
Noortje de Haan, Karli R Reiding, Jasminka Krištić, Agnes L Hipgrave Ederveen, Gordan Lauc, Manfred Wuhrer
N-linked glycosylation of the fragment crystallizable (Fc)-region of immunoglobulin G (IgG) is known to have a large influence on the activity of the antibody, an effect reported to be IgG subclass specific. This situation applies both to humans and mice. The mouse is often used as experimental animal model to study the effects of Fc-glycosylation on IgG effector functions, and results are not uncommonly translated back to the human situation. However, while human IgG Fc-glycosylation has been extensively characterized in both health and disease, this is not the case for mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28614908/adenoviral-production-of-interleukin-2-at-the-tumor-site-removes-the-need-for-systemic-postconditioning-in-adoptive-cell-therapy
#12
Joao Manuel Santos, Riikka Havunen, Mikko Siurala, Víctor Cervera-Carrascon, Siri Tähtinen, Suvi Sorsa, Marjukka Anttila, Pauliina Karell, Anna Kanerva, Akseli Hemminki
Systemic high dose interleukin-2 (IL-2) postconditioning has long been utilized in boosting the efficacy of T cells in adoptive cell therapy (ACT) of solid tumors. The resulting severe off-target toxicity of these regimens renders local production at the tumor an attractive concept with possible safety gains. We evaluated the efficacy and safety of intratumorally administered IL-2-coding adenoviruses in combination with tumor-infiltrating lymphocyte therapy in syngeneic Syrian hamsters bearing HapT1 pancreatic tumors and with T cell receptor transgenic ACT in B16...
June 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28614145/non-human-primate-rhesus-macaque-models-of-severe-pressure-targeted-hemorrhagic-and-poly-traumatic-hemorrhagic-shock
#13
Forest R Sheppard, Antoni R Macko, Jacob J Glaser, Philip J Vernon, Alexander J Burdette, R Madelaine Paredes, Craig A Koeller, Anthony E Pusateri, Douglas K Tadaki, Sylvain Cardin
BACKGROUND: We endeavored to develop clinically translatable non-human primate (NHP) models of severe poly-traumatic hemorrhagic shock. METHODS: NHPs were randomized into five pressure-targeted severe hemorrhagic shock (PTHS) ± additional injuries scenarios: 30-min PTHS (PTHS-30), 60-min PTHS (PTHS-60), PTHS-60 + soft tissue injury (PTHS-60+ST), PTHS-60+ST + femur fracture (PTHS-60+ST+FF) and decompensated PTHS+ST+FF (PTHS-D). Physiologic parameters were recorded and blood samples collected at five time points with animal observation through T = 24hrs...
June 13, 2017: Shock
https://www.readbyqxmd.com/read/28611475/murine-lrba-deficiency-causes-ctla-4-deficiency-in-tregs-without-progression-to-immune-dysregulation
#14
Deborah Burnett, Ian Parish, Etienne Masle-Farquhar, Robert Brink, Christopher Goodnow
Inherited mutations in Lipopolysaccharide Responsive Beige-like Anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B cell and antibody deficiency (common variable immunodeficiency, CVID), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells, and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9-mediated gene targeting...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28611474/p38%C3%AE-regulates-cytokine-induced-ifn%C3%AE-secretion-via-the-mnk1-eif4e-pathway-in-th1-cells
#15
María Salvador-Bernáldez, Sara B Mateus, Iván Del Barco Barrantes, Simon C Arthur, Carlos Martínez-A, Angel R Nebreda, Jesús M Salvador
The p38 mitogen-activated protein kinase (MAPK) pathway is involved in the regulation of immune and inflammatory processes. We used p38α-conditional, p38β-deficient, and p38α/β double-null mouse models to address the role of these two p38 MAPK in CD4(+) T cells, and found that p38α deficiency causes these cells to hyperproliferate. Our studies indicate that both p38α and p38β are dispensable for T helper cell type 1 (Th1) differentiation but, by controlling IFNγ and TNFα production, are critical for normal Th1 effector function...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28608562/t11ts-immunotherapy-repairs-pi3k-akt-signaling-in-t-cells-clues-towards-enhanced-t-cell-survival-in-rat-glioma-model
#16
Suhnrita Chaudhuri, Manoj Kumar Singh, Debanjan Bhattacharya, Ankur Datta, Iman Hazra, Somnath Mondal, Omar Faruk Sk Md, Larance Ronsard, Tushar Kanti Ghosh, Swapna Chaudhuri
Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T-cell defense and T-cell survival. One of the chief contributors to T-cell survival downstream of activation is the PI3K-AKT pathway. Our prior studies showed that the novel immunotherapeutic molecule T11-target structure (T11TS) blocks T-cell apoptosis in glioma. We also showed activation of immunological synapse components and calcineurin-NFAT pathway following T11TS immunotherapy of glioma-bearing rats...
June 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28603460/cultivating-the-multiple-sclerosis-workforce-of-the-future
#17
Gabriele C DeLuca, Guy Buckle, Irene Cortese, Jennifer S Graves, June Halper, Scott D Newsome, Nancy Sicotte, Corey C Ford
Multiple sclerosis (MS) is a complex neurologic disorder that affects people with ever-changing needs. The MS health-care field has entered an era of exponential knowledge growth in which better understanding of the immunologic dysregulation of the disease has translated into an expanding array of treatment options. It is estimated that, if it has not already, within the next decade the demands of a growing MS patient population will outstrip the number of professionals dedicated to the management of this chronic, lifelong disease...
May 2017: International Journal of MS Care
https://www.readbyqxmd.com/read/28597146/human-i%C3%AE%C2%BAb%C3%AE-gain-of-function-a-severe-and-syndromic-immunodeficiency
#18
REVIEW
Bertrand Boisson, Anne Puel, Capucine Picard, Jean-Laurent Casanova
Germline heterozygous gain-of-function (GOF) mutations of NFKBIA, encoding IκBα, cause an autosomal dominant (AD) form of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Fourteen unrelated patients have been reported since the identification of the first case in 2003. All mutations enhanced the inhibitory activity of IκBα, by preventing its phosphorylation on serine 32 or 36 and its subsequent degradation. The mutation certainly or probably occurred de novo in 13 patients, whereas it was inherited from a parent with somatic mosaicism in one patient...
July 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28592764/multiple-myeloma-pathophysiology-and-progress-in-management
#19
Junya Kuroda, Yoshiaki Chinen
There have been dramatic recent advances in understanding the basic pathophysiology and treatment strategies for multiple myeloma (MM). Research has shown both a high inter-patient diversity and intra-clonal heterogeneity even in a single patient in terms of cytogenetic/molecular abnormalities, and has also identified marked diversity in the immunological factors involved in tumor surveillance among MM patients. In the presence of a variety of novel agents, including molecular-targeted agents, immunomodulatory agents, and monoclonal antibodies, the optimal translation of current knowledge on both molecular and immunologic findings into clinical use is crucial for managing MM...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28589521/strengthening-the-case-for-epilepsy-drug-development-bridging-experiences-from-the-alzheimer-s-disease-field-an-opinion
#20
Roy E Twyman
Given the sheer number of drugs (over 20!) available for treatment of seizures, epilepsy can be considered one of the most successful areas in pharmaceutical development and especially for neuroscience. However, despite the large number of drug treatment options available for managing patients with epilepsy, there remains considerable unmet need. For example, the overall impact on seizure control has not been substantial with approximately 30% of patients remaining refractory or their seizures not adequately controlled...
July 2017: Neurochemical Research
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