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https://www.readbyqxmd.com/read/29792808/eradication-of-established-tumors-by-chemically-self-assembled-nanoring-csan-targeted-t-cells
#1
Jacob Petersburg, Jingjing Shen, Clifford M Csizmar, Katherine A Murphy, Justin Spanier, Kari Gabrielse, Thomas S Griffith, Brian Fife, Carston R Wagner
Our laboratory has developed chemically self-assembled nanorings (CSANs) as prosthetic antigen receptors (PARs) for the non-genetic modification of T-cell surfaces. PARs have been successfully employed in vitro to activate T cells for the selective killing of leukemia cells. However, PAR efficacy has yet to be evaluated in vivo or against solid tumors. Therefore, we developed bispecific PARs that selectively target the human CD3 receptor and human Epithelial Cell Adhesion Molecule (EpCAM), which is overexpressed on multiple carcinomas and cancer stem cells...
May 24, 2018: ACS Nano
https://www.readbyqxmd.com/read/29792135/modified-ldl-immune-complexes-and-cardiovascular-disease
#2
Maria F Lopes-Virella, Gabriel Virella
Modified forms of LDL, both spontaneously formed in the organism or prepared in the laboratory, are immunogenic. As a consequence, antigen-antibody complexes (immune complexes, IC) formed in vivo can be measured in the peripheral blood, and their levels are strong predictors of cardiovascular disease (CVD). It has been possible to generate antibodies that recognize different LDL modifications, allowing the analysis of circulating IC constitution. Clinical studies showed that the antigenic constitution of the IC has a modulating effect on the development of CVD...
May 23, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29791435/immunogenicity-and-efficacy-following-sequential-parenterally-administered-doses-of-salmonella-enteritidis-cops-flic-glycoconjugates-in-infant-and-adult-mice
#3
Scott M Baliban, Brittany Curtis, Deanna Toema, Sharon M Tennant, Myron M Levine, Marcela F Pasetti, Raphael Simon
In sub-Saharan Africa, invasive nontyphoidal Salmonella (iNTS) infections with serovars S. Enteritidis, S. Typhimurium and I 4,[5],12:i:- are widespread in children < 5 years old. Development of an efficacious vaccine would provide an important public health tool to prevent iNTS disease in this population. Glycoconjugates of S. Enteritidis core and O-polysaccharide (COPS) coupled to the homologous serovar phase 1 flagellin protein (FliC) were previously shown to be immunogenic and protected adult mice against death following challenge with a virulent Malian S...
May 23, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29791318/the-inhibitors-a-challenge-for-the-management-of-patients-with-hereditary-haemophilia-a
#4
Romeo-Gabriel Mihăilă
INTRODUCTION: Our research strategy was aimed at evaluating the possible implication of the type of factor VIII product administered as substitution treatment to haemophilia A patients in the occurrence of inhibitors and their consequences on the management. METHODS: Scientific articles from July 2015 to July 2017 were searched using the PubMed and PubMed Central databases. The used search terms included "haemophilia A", "inhibitors", "plasma-derived factor VIII" and "recombinant factor VIII"...
May 1, 2018: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
https://www.readbyqxmd.com/read/29791241/neutrophil-mediated-delivery-of-pixantrone-loaded-liposomes-decorated-with-poly-sialic-acid-octadecylamine-conjugate-for-lung-cancer-treatment
#5
Xiang Luo, Ling Hu, Huangliang Zheng, Mingqi Liu, Xinrong Liu, Cong Li, Qiujun Qiu, Zitong Zhao, Xiaobo Cheng, Chaoyang Lai, Yuqing Su, Yihui Deng, Yanzhi Song
Poly(sialic acid) (PSA) is a natural hydrophilic biodegradable and non-immunogenic biopolymer, receptors for its monomer are expressed on peripheral blood neutrophils (PBNs), which plays important roles in the progression and invasion of tumors. A poly(sialic acid)-octadecylamine conjugate (PSA-ODA) was synthesized and then anchor it on the surface of liposomal pixantrone (Pix-PSL), to achieve an improved anticancer effect. The liposomes were prepared using a remote loading method via a pH gradient, and then assessed for particle size, zeta potential encapsulation efficiency, in vitro release, and in vitro cytotoxicity...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29789417/mapping-the-hla-ligandome-of-colorectal-cancer-reveals-an-imprint-of-malignant-cell-transformation
#6
Markus W Löffler, Daniel J Kowalewski, Linus Backert, Jörg Bernhardt, Patrick Adam, Heiko Schuster, Florian Dengler, Daniel Backes, Hans-Georg Kopp, Stefan Beckert, Silvia Wagner, Ingmar Königsrainer, Oliver Kohlbacher, Lothar Kanz, Alfred Königsrainer, Hans-Georg Rammensee, Stefan Stevanovic, Sebastian P Haen
Immune cell infiltrates have proven highly relevant for colorectal carcinoma (CRC) prognosis, making CRC a promising candidate for immunotherapy. Since tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here we comprehensively describe the naturally presented HLA-ligandome of CRC and corresponding non-malignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA-class I ligands on CRC and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29789243/menacwy-tt-is-immunogenic-when-co-administered-with-tdap-and-as04-hpv16-18-in-girls-and-young-women-results-from-a-phase-iii-randomized-trial
#7
Luis Rivera, Pornthep Chanthavanich, Airi Põder, P V Suryakiran, Archana Jastorff, Marie Van der Wielen
BACKGROUND: Co-administration of vaccines in adolescents may improve coverage. We assessed co-administration of quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT), human papillomavirus 16/18 AS04-adjuvanted vaccine (AS04-HPV16/18) and tetanus-diphtheria-acellular pertussis vaccine (Tdap) in girls and young women. METHODS: In this phase IIIb study (NCT01755689), 1300 healthy 9-25-year-old females were randomized (1:1:1:1:1) to receive: MenACWY-TT at month (M) 0 and AS04-HPV16/18 at M1, M2, M7; MenACWY-TT and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; AS04-HPV16/18 at M0, M1, M6; MenACWY-TT, Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6...
May 19, 2018: Vaccine
https://www.readbyqxmd.com/read/29789238/a-phase-1-study-of-safety-and-immunogenicity-following-intradermal-administration-of-a-tetravalent-dengue-vaccine-candidate
#8
Lisa A Jackson, Richard Rupp, Athanasia Papadimitriou, Derek Wallace, Marsha Raanan, Kelley J Moss
BACKGROUND: As part of the ongoing search for an effective dengue vaccine, Takeda performed a phase 1b study to investigate the safety and immunogenicity of an early low-dose tetravalent dengue vaccine candidate formulation (LD-TDV), based on an attenuated serotype 2 backbone, when administered intradermally with an injector device (PharmaJet®), or needle-syringe. METHODS: The study was performed in two centers in the US, in healthy 18-45 year old subjects with no history of dengue vaccination or disease...
May 19, 2018: Vaccine
https://www.readbyqxmd.com/read/29788338/clinical-pharmacology-in-adult-and-pediatric-inflammatory-bowel-disease
#9
Amy Hemperly, William J Sandborn, Niels Vande Casteele
This review describes the clinical pharmacology of the major drugs used for the treatment of patients with inflammatory bowel disease (IBD). Pharmacokinetics, drug metabolism, mechanism of action, efficacy, and safety profile are discussed. Some small molecules were developed to act systemically (eg, ozanimod) or locally (eg, aminosalicylates) and thus have disparate pharmacokinetic properties. In addition, locally acting compounds have been optimized to mitigate systemic exposure-eg, budesonide, which undergoes extensive first-pass metabolism-thereby reducing systemic bioavailability and side effects...
May 17, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29785172/graft-versus-host-disease-from-basic-pathogenic-principles-to-dna-damage-response-and-cellular-senescence
#10
REVIEW
Adam Kuba, Ludek Raida
Graft versus host disease (GVHD), a severe immunogenic complication of allogeneic hematopoietic stem cell transplantation (HSCT), represents the most frequent cause of transplant-related mortality (TRM). Despite a huge progress in HSCT techniques and posttransplant care, GVHD remains a significant obstacle in successful HSCT outcome. This review presents a complex summary of GVHD pathogenesis with focus on references considering basic biological processes such as DNA damage response and cellular senescence.
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29784954/the-structural-basis-of-nanobody-unfolding-reversibility-and-thermoresistance
#11
Patrick Kunz, Katinka Zinner, Norbert Mücke, Tanja Bartoschik, Serge Muyldermans, Jörg D Hoheisel
Nanobodies represent the variable binding domain of camelid heavy-chain antibodies and are employed in a rapidly growing range of applications in biotechnology and biomedicine. Their success is based on unique properties including their reported ability to reversibly refold after heat-induced denaturation. This view, however, is contrasted by studies which involve irreversibly aggregating nanobodies, asking for a quantitative analysis that clearly defines nanobody thermoresistance and reveals the determinants of unfolding reversibility and aggregation propensity...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784854/molecular-subtype-specific-immunocompetent-models-of-high-grade-urothelial-carcinoma-reveal-differential-neoantigen-expression-and-response-to-immunotherapy
#12
Ryoichi Saito, Christof C Smith, Takanobu Utsumi, Lisa M Bixby, Jordan Kardos, Sara E Wobker, Kyle G Stewart, Shengjie Chai, Ujjawal Manocha, Kevin Matthew Byrd, Jeffrey S Damrauer, Scott E Williams, Benjamin G Vincent, William Y Kim
High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like and basal-like subtypes. We describe here the first subtype-specific murine models of bladder cancer and show that Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL: luminal-like) and BBN (basal-like) tumors are more faithful to human bladder cancer than the widely-used MB49 cells. Following engraftment into immunocompetent C57BL/6 mice, BBN tumors were more responsive to PD-1 inhibition than UPPL tumors...
May 21, 2018: Cancer Research
https://www.readbyqxmd.com/read/29784675/radiation-followed-by-ox40-stimulation-drives-local-and-abscopal-antitumor-effects-in-an-anti-pd1-resistant-lung-tumor-model
#13
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29784645/harnessing-post-translational-modifications-for-next-generation-hiv-immunogens
#14
REVIEW
Joel D Allen, Rogier W Sanders, Katie J Doores, Max Crispin
The extensive post-translational modifications of the envelope spikes of the human immunodeficiency virus (HIV) present considerable challenges and opportunities for HIV vaccine design. These oligomeric glycoproteins typically have over 30 disulfide bonds and around a 100 N-linked glycosylation sites, and are functionally dependent on protease cleavage within the secretory system. The resulting mature structure adopts a compact fold with the vast majority of its surface obscured by a protective shield of glycans which can be targeted by broadly neutralizing antibodies (bnAbs)...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29784470/immunogenicity-and-safety-of-menacwy-tt-a-meningococcal-conjugate-vaccine-co-administered-with-routine-childhood-vaccine-in-healthy-infants-a-phase-iii-randomized-study
#15
Ghassan Dbaibo, Juan Carlos Tinoco Favila, Magali Traskine, Archana Jastorff, Marie Van der Wielen
BACKGROUND: Invasive meningococcal disease has a high burden in young children, particularly during infancy. We investigated the immunogenicity and safety of a quadrivalent meningococcal conjugated vaccine (MenACWY-TT) co-administered with routine vaccines in healthy infants. METHODS: In this phase IIIb study (NCT01340898) conducted in 2 centers in Lebanon and Mexico, 750 infants were randomized (2:1:1) to receive MenACWY-TT according to 3 schedules: 3+1 (at ages 2, 4, 6 and 15-18 months; group ACWY3+1); 1+1 (at 6 and 15-18 months; group ACWY1+1) or single-dose at 15-18 months (group ACWY1)...
May 18, 2018: Vaccine
https://www.readbyqxmd.com/read/29784469/duration-of-post-vaccination-immunity-to-yellow-fever-in-volunteers-eight-years-after-a-dose-response-study
#16
Reinaldo de Menezes Martins, Maria de Lourdes S Maia, Sheila Maria Barbosa de Lima, Tatiana Guimarães de Noronha, Janaina Reis Xavier, Luiz Antonio Bastos Camacho, Elizabeth Maciel de Albuquerque, Roberto Henrique Guedes Farias, Thalita da Matta de Castro, Akira Homma
In 2009, Bio-Manguinhos conducted a dose-response study with the yellow fever vaccine, administering the vaccine in the usual mean dose of 27,476 IU (full dose, reference) and in tapered doses (10,447 IU, 3013 IU, 587 IU, 158 IU, and 31 IU) by the usual subcutaneous route and usual volume (0.5 mL). Tapered doses were obtained by dilution in the manufacturer's laboratory, and the test batches presented industrial quality. Doses down to 587 IU showed similar immunogenicity to the full dose (27,476, reference), while the 158 IU and 31 IU doses displayed lower immunogenicity...
May 18, 2018: Vaccine
https://www.readbyqxmd.com/read/29784457/the-dynamic-role-of-dengue-cross-reactive-immunity-changing-the-approach-to-defining-vaccine-safety-and-efficacy
#17
REVIEW
Kathryn B Anderson, Timothy P Endy, Stephen J Thomas
Dengue virus infections cause a substantial public health burden in tropical and subtropical regions. A single dengue vaccine has been approved by regulatory authorities in 19 countries, but concerns regarding vaccine safety in people who are dengue naive at the time of immunisation has introduced uncertainty into the vaccine's future. As other dengue vaccines complete or enter large-scale efficacy trials, we argue that foundational work by Sabin, historic epidemiological observations of dengue outbreaks, and prospective cohort studies in Asia and the Americas indicate that modifications must be made to the methods of assessing dengue vaccines...
May 18, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29783682/heat-shock-gene-inactivation-and-protein-aggregation-with-links-to-chronic-diseases
#18
Ian James Martins
The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer's disease...
May 18, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29783025/immunogenicity-and-reactogenicity-of-high-versus-standard-dose-trivalent-inactivated-influenza-vaccine-in-healthcare-workers-a-pilot-randomized-controlled-trial
#19
C Volling, B L Coleman, K Katz, A E Simor, M Muller, J Powis, J McElhaney, A McGeer
OBJECTIVES: To compare immunogenicity, reactogenicity and acceptability of high- and standard-dose trivalent inactivated influenza vaccine (HDTIV, SDTIV) in 18-64 year olds. METHODS: We randomized 18-64-year-olds to HDTIV or SDTIV in two consecutive years. We collected serum on Days 0 and 21, measured hemagglutination inhibition (HAI) titers, and compared seroconversion, Day 21 titers, seroprotection, reactogenicity, acceptability. RESULTS: Immunogenicity was evaluable in 42 of 47 2014 participants, all 33 both year participants, and 87 of 90 2015-only participants...
May 18, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29782675/hierarchical-micro-nanostructures-from-human-hair-for-biomedical-applications
#20
Di-Wei Zheng, Sheng Hong, Lu Xu, Chu-Xin Li, Ke Li, Si-Xue Cheng, Xian-Zheng Zhang
With the prominent progress of biomedical engineering, materials with high biocompatibility and versatile functions are urgently needed. So far, hierarchical structures in nature have shed some light on the design of high performance materials both in concept and implementation. Inspired by these, the hierarchical micro-/nanostructures of human hair are explored and human hair is further broken into hierarchical microparticles (HMP) and hierarchical nanoparticles (HNP) with top-down procedures. Compared with commercialized carriers, such as liposomes or albumin nanoparticles, the obtained particles exhibit high hemocompatibility and negligible immunogenicity...
May 21, 2018: Advanced Materials
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