The Development of a Vaccine Against Meningococcus B Using Reverse Vaccinology
Discussion
The licensure in 2013 of the four component MenB vaccine (Bexsero) was the culmination of a scientific collaboration between university and industry-based scientists. The former provided cutting edge genomic, genetic, and clinical trials expertise; the latter undertook the vital high-throughput, “brute force” evaluation of hundreds of candidate antigens discovered through genomics, the in-depth characterization of the functional and immunological properties of the selected vaccine antigens and then stage-managed the pre-clinical and clinical testing required to obtain licensure. The facilitating...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research
Materials and Information Flow Analysis and Optimization of Manufacturing Processes in MSMEs by the Application of Value Stream Mapping (VSM) Technique
Publication date: 2018Source: Materials Today: Proceedings, Volume 5, Issue 14, Part 2Author(s): Harpreet Singh, Ankur Bahl, Anil Kumar, Guravtar Singh MannAbstractValue stream is a set of all the specified actions of process (s) for product (s) which are required to convert the raw material into finished product and all the steps through which material has to travel from stage of raw material to become finished goods. After initial research, the group of small enterprises was selected and work was started on them. It is out of which two of them are of same product family and another two produce different types of product....
Source: Materials Today: Proceedings - December 22, 2018 Category: Materials Science Source Type: research
£26m spent on private consultancy firms to aid NHS reorganisation, BMA finds
(Source: BMJ News)
Source: BMJ News - December 18, 2018 Category: General Medicine Source Type: research
Leadless Pacemaker Implantation – is it possible to eliminate pericardial effusion as a complication?
Paul Roberts has received honoraria from Medtronic for consultancy and speakers bureau. (Source: Heart Rhythm)
Source: Heart Rhythm - December 18, 2018 Category: Cardiology Authors: Paul R. Roberts Source Type: research
Multiple-therapy-resistant major depressive disorder: a clinically important concept.
Authors: McAllister-Williams RH, Christmas DMB, Cleare AJ, Currie A, Gledhill J, Insole L, Malizia AL, McGeever M, Morriss R, Robinson LJ, Scott M, Stokes PRA, Talbot PS, Young AH
Abstract
SummaryMany novel therapeutic options for depression exist that are either not mentioned in clinical guidelines or recommended only for use in highly specialist services. The challenge faced by clinicians is when it might be appropriate to consider such 'non-standard' interventions. This analysis proposes a framework to aid this decision.Declaration of interestIn the past 3 years R.H.M.W. has received support for researc...
Source: The British Journal of Psychiatry for Mental Science - December 6, 2018 Category: Psychiatry Tags: Br J Psychiatry Source Type: research
Realizing Effectiveness across Continents with Hydroxyurea (REACH): A Prospective Multi-National Trial of Hydroxyurea for Sickle Cell Anemia in Sub-Saharan Africa
Hydroxyurea is a potent and safe disease-modifying therapy for sickle cell anemia (SCA), with available data proving laboratory and clinical efficacy for both children and adults. Although the global burden of SCA is greatest within sub-Saharan Africa, almost all studies with hydroxyurea to date have been conducted in the US and Europe. Since additional comorbidities may affect children with SCA in low-resource settings, including malnutrition, malaria, and other infections, prospective research is needed to develop locally appropriate guidelines for hydroxyurea use.To assess the feasibility, safety, and benefits of hydrox...
Source: Blood - November 21, 2018 Category: Hematology Authors: Tshilolo, L., Tomlinson, G., Williams, T. N., Santos, B., Olupot-Olupot, P., Lane, A., Aygun, B., Stuber, S., Latham, T., McGann, P. T., Ware, R. E. Tags: Plenary Scientific Session Source Type: research
Memory-Like Natural Killer Cells
This study demonstrated that rel/ref AML patients were able to safely receive IL-12/15/18-activated donor NK cells (up to 10x106/kg) without developing cytokine release syndrome, neurotoxicity, or graft-versus-host disease. Immune monitoring revealed that memory-like NK cells expanded, trafficked to the bone marrow, and exhibited enhanced anti-leukemia function ex vivo. Clinical responses (CR/CRi) were observed in >50% of patients with active rel/ref AML.11 Ongoing studies are exploring memory-like NK cell adoptive immunotherapy in a phase 2 trial for rel/ref AML, combined with same-donor allogeneic hematopoietic cell t...
Source: Blood - November 21, 2018 Category: Hematology Authors: Berrien-Elliott, M. M., Wagner, J. A., Cashen, A. F., Fehniger, T. A. Tags: The Making of Memory Source Type: research
Contribution of Amino Acid Metabolism to Hematologic Malignancies
Tumor cells rewire metabolic pathways to meet the high metabolic demands of proliferation, frequently developing auxotrophy to specific amino acid(s) (AAs) required to satisfy protein biosynthesis. Thus specific metabolic inhibitors or AA-depleting enzymes have been developed and tested as cancer therapeutics. For example, depletion of asparagine by bacterial L-asparaginase (ASNase) has proven efficacious against hematologic malignancies, especially leukemia and lymphoma, by starving tumors lacking asparagine synthetase (ASNS). We and others have reported that the glutaminase (GLS) activity of ASNase is required for antica...
Source: Blood - November 21, 2018 Category: Hematology Authors: Konopleva, M. Y., Lorenzi, P. L., Ghotbaldini, S., Tabe, Y., Cai, T., Tiziani, S. Tags: Metabolism and Hematologic Malignancies Source Type: research
Mitochondrial Dysfunction in Normal and Malignant Hematopoiesis
AML (Acute Myeloid Leukemia) is an aggressive hematologic malignancy with a high rate of relapse. Therefore, it is important to identify novel therapeutic strategies for patients with this disease. We and others have shown that AML cells and stem cells have a unique reliance on mitochondrial oxidative metabolism and are highly vulnerable to strategies that target mitochondrial pathways. This unique vulnerability is due, at least in part, to increased flux of metabolites into the TCA (Kreb's) cycle that results in increased rates of oxidative metabolism and reduced space reserve capacity (the difference between basal and ma...
Source: Blood - November 21, 2018 Category: Hematology Authors: Schimmer, A. Tags: Metabolism and Hematologic Malignancies Source Type: research
Human Pluripotent Stem Cell-Derived Blood Cells for Therapies
It has now been twenty years since human embryonic stem cells (hESCs) were first isolated and described in 1998. In the next decade, induced pluripotent stem cells (iPSCs) were produced first from mouse somatic cells and then from human cells. Since these landmark advances, hESCs and iPSCs have been utilized to advance our understanding of basic human developmental biology and cellular plasticity. These lessons are crucial to fulfill the goal to use human pluripotent stem cells to derive new cellular therapies to better treat and repair organs and tissues damaged by disease, trauma or aging. Clinical trials are underway to...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kaufman, D. S. Tags: De Novo Generation of Blood and Progenitor Cells Source Type: research
Chromatin State and Immunotherapy
The functional impairment of T cell-mediated immunity within the tumor microenvironment (TME) is a defining feature of many cancers. Checkpoint blockade therapy seeks to reinvigorate T cell responses by targeting inhibitory receptors such as PD-1, which are upregulated by dysfunctional TILs. However, the fundamental mechanisms underlying T cell dysfunction in the TME remain poorly understood, as are the mechanisms by which checkpoint blockade overcomes this dysfunction. Initial studies of dysfunctional CD8+ T cells in both human and mouse tumors suggested that they share features of T cell exhaustion, including co-inhibito...
Source: Blood - November 21, 2018 Category: Hematology Authors: Haining, W. N. Tags: Epigenetic and Genomic Determinants in Cancer Immunotherapy Source Type: research
Neoepitope Discovery
Our previous work led to the elaboration of the cancer immunoediting concept wherein the immune system was shown to not only protect individuals against cancer outgrowth but also shape tumor immunogenicity. In the course of these studies we developed an immunogenomics approach involving identification of expressed somatic mutations in tumors and prediction of those mutations that formed tumor-specific mutant neoantigens (TSMA). We went on to show that some of the predicted strong neoantigens expressed in highly immunogenic, unedited tumor cells (derived from immunodeficient mice) were important cancer immunoediting targets...
Source: Blood - November 21, 2018 Category: Hematology Authors: Schreiber, R. D. Tags: Epigenetic and Genomic Determinants in Cancer Immunotherapy Source Type: research
JNJ-64179375 Inhibits Exosite I-Mediated Thrombin Activity While Preserving Exosite II and Active Site Function in Vitro
Anticoagulation requires a careful balance to achieve antithrombotic efficacy without disrupting normal hemostasis. Although current generation direct oral anticoagulants (DOACs) offer advantages over traditional warfarin or heparin therapy they still carry a bleeding risk, highlighting an unmet need for novel anticoagulants with improved therapeutic indices. DOACs such as apixaban and dabigatran bind to the active sites of their target proteases thereby inhibiting proteolysis of all substrates. In contrast, the recombinant antibody JNJ-64179375 (JNJ-9375) specifically binds to the exosite I region of thrombin without inhi...
Source: Blood - November 21, 2018 Category: Hematology Authors: Bunce, M., Chintala, M., Krishnaswamy, S., Bradford, H. N. Tags: 321. Blood Coagulation and Fibrinolytic Factors: Structural Biology of Coagulation Proteins Source Type: research
Microbiota and Neutrophil Development
Microbiota, Neutrophil Development, and Sickle Cell Disease PathogenesisPaul S. FrenetteRuthL. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, USAReal-time intravital microscopy analyses in humanized models of sickle cell disease (SCD) have uncovered a critical role for neutrophils in mediating vaso-occlusive episodes. Peripheral blood neutrophils are recruited in inflamed venules via the interactions of the selectin adhesion molecules (E- and P-selectin) with their ligands. These molecules mediate neutrophil rolling on the vessel wall allowi...
Source: Blood - November 21, 2018 Category: Hematology Authors: Frenette, P. S. Tags: Regulation of Myelopoiesis by Inflammatory Signaling Source Type: research
Genetic Heterogeneity and Evolution in Lymphoid Malignancies
Patterns of mutation and clonal evolution in relapsed acute lymphoblastic leukemiaRelapsed acute lymphoblastic leukemia remains a major cause of childhood cancer death, and this remains true despite the advent of new targeted and immunotherapeutic approaches. Recent years have witnessed the use of broad and deep serial genomic profiling approaches to dissect the relationship of genetic variegation to clonal evolution and relapse. Studies of over 90 children treated on St Jude Total Therapy protocols, incorporating genome, exome and transcriptome sequencing, coupled with limiting dilution xenografting to formally elucidate ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mullighan, C. G. Tags: Role and Mechanisms of Clonal Evolution in Lymphoid Malignancies Source Type: research
