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https://www.readbyqxmd.com/read/30305501/-incorporation-of-novel-agents-into-the-treatment-for-acute-myeloid-leukemia
#1
Takahiro Yamauchi
The mainstay of therapeutic modalities of acute myeloid leukemia (AML) includes intensive chemotherapies and allogeneic hematopoietic cell transplantation. The gold standard of the induction treatment is a regular dose of cytarabine plus anthracycline, and several courses of consolidation therapy are administered. Allogeneic hematopoietic cell transplantation is employed in patients with intermediate-poor risks. No new drugs have been introduced to the treatment of AML for nearly 30 years. However, in 2017, the US Food and Drug Administration approved four novel drugs for treating AML: FLT3 inhibitor midostaurin, IDH2 inhibitor enasidenib, liposomal cytarabine-daunorubicin CPX-351, and revived antibody-drug conjugate gemtuzumab ozogamicin...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/30302283/system-immunology-based-identification-of-blood-transcriptional-modules-correlating-to-antibody-responses-in-sheep
#2
Roman Othmar Braun, Livia Brunner, Kurt Wyler, Gaël Auray, Obdulio García-Nicolás, Sylvie Python, Beatrice Zumkehr, Véronique Gaschen, Michael Hubert Stoffel, Nicolas Collin, Christophe Barnier-Quer, Rémy Bruggmann, Artur Summerfield
Inactivated vaccines lack immunogenicity and therefore require potent adjuvants. To understand the in vivo effects of adjuvants, we used a system immunology-based analysis of ovine blood transcriptional modules (BTMs) to dissect innate immune responses relating to either antibody or haptoglobin levels. Using inactivated foot-and-mouth disease virus as an antigen, we compared non-adjuvanted to liposomal-formulated vaccines complemented or not with TLR4 and TLR7 ligands. Early after vaccination, BTM relating to myeloid cells, innate immune responses, dendritic cells, and antigen presentation correlated positively, whereas BTM relating to T and natural killer cells, as well as cell cycle correlated negatively with antibody responses...
2018: NPJ Vaccines
https://www.readbyqxmd.com/read/30302281/a-combination-of-tlr-4-agonist-and-saponin-adjuvants-increases-antibody-diversity-and-protective-efficacy-of-a-recombinant-west-nile-virus-antigen
#3
Neal Van Hoeven, Steven Wiley, Emily Gage, Andrew Fiore-Gartland, Brian Granger, Sean Gray, Christopher Fox, David E Clements, D Elliot Parks, Scott Winram, Dan T Stinchcomb, Steven G Reed, Rhea N Coler
Members of the Flaviviridae family are the leading causes of mosquito-borne viral disease worldwide. While dengue virus is the most prevalent, the recent Zika virus outbreak in the Americas triggered a WHO public health emergency, and yellow fever and West Nile viruses (WNV) continue to cause regional epidemics. Given the sporadic nature of flaviviral epidemics both temporally and geographically, there is an urgent need for vaccines that can rapidly provide effective immunity. Protection from flaviviral infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions...
2018: NPJ Vaccines
https://www.readbyqxmd.com/read/30297818/a-malaria-vaccine-adjuvant-based-on-recombinant-antigen-binding-to-liposomes
#4
Wei-Chiao Huang, Bingbing Deng, Cuiyan Lin, Kevin A Carter, Jumin Geng, Aida Razi, Xuedan He, Upendra Chitgupi, Jasmin Federizon, Boyang Sun, Carole A Long, Joaquin Ortega, Sheetij Dutta, C Richter King, Kazutoyo Miura, Shwu-Maan Lee, Jonathan F Lovell
Pfs25 is a malaria transmission-blocking vaccine antigen candidate, but its apparently limited immunogenicity in humans has hindered clinical development. Here, we show that recombinant, polyhistidine-tagged (his-tagged) Pfs25 can be mixed at the time of immunization with pre-formed liposomes containing cobalt porphyrin-phospholipid, resulting in spontaneous nanoliposome antigen particleization (SNAP). Antigens are stably presented in uniformly orientated display via his-tag insertion in the cobalt porphyrin-phospholipid bilayer, without covalent modification or disruption of antigen conformation...
October 8, 2018: Nature Nanotechnology
https://www.readbyqxmd.com/read/30291987/lipid-conjugation-of-tlr7-agonist-resiquimod-ensures-co-delivery-with-the-liposomal-cationic-adjuvant-formulation-01-caf01-but-does-not-enhance-immunopotentiation-compared-to-non-conjugated-resiquimod-caf01
#5
Alexander Wilkinson, Eric Lattmann, Carla B Roces, Gabriel Pedersen, Dennis Christensen, Yvonne Perrie
Pattern recognition receptors, including the Toll-like receptors (TLRs), are important in the induction and activation of two critical arms of the host defence to pathogens and microorganisms; the rapid innate immune response (as characterised by the production of Th1 promoting cytokines and type 1 interferons) and the adaptive immune response. Through this activation, ligands and agonists of TLRs can enhance immunotherapeutic efficacy. Resiquimod is a small (water-soluble) agonist of the endosome-located Toll-like receptors 7 and 8 (TLR7/8)...
October 3, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30290888/quantification-of-toxoplasma-gondii-in-the-tissues-of-balb-c-mice-after-immunization-with-nanoliposomal-excretory-secretory-antigens-using-real-time-pcr
#6
Yaghob Azadi, Ehsan Ahmadpour, Hamed Hamishehkar, Ahmad Daryani, Adel Spotin, Mahmoud Mahami-Oskouei, Aleksandra Barac, Saba Rajabi, Paria Alizadeh, Mahbobeh Montazeri
BACKGROUND: Toxoplasmosis is an infectious disease caused by the intracellular parasite Toxoplasma gondii. Although almost 1/3 of the world's population are seropositive, there is no effective vaccine against toxoplasmosis. Therefore, the development of an effective vaccine for control of toxoplasmosis is one of major concerns in parasitology. The aim of this study was to evaluate the efficacy of nano-liposomal excretory-secretory antigens (NLESA) in BALB/c mice. MATERIALS AND METHODS: Excretory-secretory antigens (ESA) was obtained from tachyzoites, encapsulated in the liposome and studied by scanning electron microscope...
August 2018: Comparative Immunology, Microbiology and Infectious Diseases
https://www.readbyqxmd.com/read/30280273/a-cell-assay-for-detecting-anti-peg-immune-response-against-peg-modified-therapeutics
#7
Taro Shimizu, Amr S Abu Lila, Mizuki Awata, Yukiyo Kubo, Yu Mima, Yosuke Hashimoto, Hidenori Ando, Keiichiro Okuhira, Yu Ishima, Tatsuhiro Ishida
PURPOSE: Immunogenicity of PEGylated proteins and nanomedicines represents a potential impediment against their development and use in clinical settings. The purpose of this study is to develop a method for detecting anti-PEG immunity of PEGylated proteins and/or nanomedicines using flow cytometry. METHODS: The binding of fluorescence-labeled mPEG-modified liposomes to HIK-G11 cells, PEG-specific hybridoma cells, or spleen cells was evaluated by flow cytometry for detecting immunogenicity of PEGylated therapeutics...
October 2, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/30266669/sortaggable-liposomes-evaluation-of-reaction-conditions-for-single-domain-antibody-conjugation-by-sortase-a-and-targeting-of-cd11b-myeloid-cells
#8
Steffen Wöll, Christopher Bachran, Stefan Schiller, Matthias Schröder, Lena Conrad, Lee Kim Swee, Regina Scherließ
Active targeting with ligand coated liposomal drug delivery systems is a means to increase the therapeutic index of drugs. Stable ligand coating requires bilayer anchorage of the commonly proteinaceous ligands and hence a conjugation of lipid structures towards amino acids. This often leads to heterogeneous reaction products especially when chemical coupling methods are employed. Chemoenzymatic Sortase-A mediated transpeptidation (sortagging) is a useful tool to avoid this protein heterogeneity through its site-specific, bioorthogonal ligation mechanism...
September 25, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/30259773/dual-character-of-gaba-action-on-cl-transport-by-the-reconstituted-cl-formula-see-text-atpase-from-rat-brain
#9
Sergey Menzikov
The Cl- /[Formula: see text]-ATPase from the plasma membranes of animal brains is an ATP-consuming Cl- -transporting ATPase P-type that is structurally coupled to GABAA receptors. The aim of work was to study the GABA effect on Cl- transport across liposomal membranes by the reconstituted ATPase under various conditions (i.e. in the absence and in the presence of ATP in the incubation medium). We reconstituted the affinity-purified enzyme in the liposomes with a fluorescent dye for Cl- . The Cl- -transport in proteoliposomes was evaluated from variations in fluorescence...
September 27, 2018: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/30249664/interferometric-plasmonic-imaging-and-detection-of-single-exosomes
#10
Yuting Yang, Guangxia Shen, Hui Wang, Hongxia Li, Ting Zhang, Nongjian Tao, Xianting Ding, Hui Yu
Exosomes play an important role in numerous cellular processes. Fundamental study and practical use of exosomes are significantly constrained by the lack of analytical tools capable of physical and biochemical characterization. In this paper, we present an optical approach capable of imaging single exosomes in a label-free manner, using interferometric plasmonic microscopy. We demonstrate monitoring of the real-time adsorption of exosomes onto a chemically modified Au surface, calculating the image intensity, and determining the size distribution...
October 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30244454/production-of-immunizing-antigen-proteoliposome-using-cell-free-protein-synthesis-system
#11
Wei Zhou, Hiroyuki Takeda
Antibodies specifically recognizing integral membrane protein are essential tool for functional analysis, diagnosis, and therapeutics targeting membrane proteins. However, development of antibodies against membrane protein remains a big challenge, because mass production of membrane protein is difficult. Recently, we developed a highly efficient cell-free production method of proteoliposome antigen using cell-free protein synthesis method with liposome and dialysis cup. Here we introduce practical and efficient integrated procedures to produce large amount of proteoliposome antigen for anti-membrane protein antibody development...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30240185/vascular-targeting-of-radiolabeled-liposomes-with-bio-orthogonally-conjugated-ligands-single-chain-fragments-provide-higher-specificity-than-antibodies
#12
Elizabeth D Hood, Colin Fred Greineder, Tea Shuvaeva, Landis Walsh, Carlos H Villa, Vladimir R Muzykantov
Liposomes are a proven, versatile and clinically viable technology platform for vascular delivery of drugs and imaging probes. Although targeted liposomes have the potential to advance these applications, complex formulations and the need for optimal affinity ligands and conjugation strategies challenge translation. Herein, we employed copper-free click chemistry functionalized liposomes to target platelet-endothelial cell adhesion molecule (PECAM-1) and intracellular adhesion molecule (ICAM-1) by conjugating clickable monoclonal antibodies (Ab) or their single chain variable fragments (scFv)...
September 21, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/30219233/prevention-of-acute-liver-injury-by-suppressing-plasma-kallikrein-dependent-activation-of-latent-tgf-%C3%AE
#13
Mengqian Li, Xian-Yang Qin, Yutaka Furutani, Ikuyo Inoue, Sanae Sekihara, Hiroyuki Kagechika, Soichi Kojima
Acute liver injury (ALI) is highly lethal acute liver failure caused by different etiologies. Transforming growth factor β (TGF-β) is a multifunctional cytokine and a well-recognized inducer of apoptotic and necrotic cell death in hepatocytes. Latent TGF-β is activated partly through proteolytic cleavage by a serine protease plasma kallikrein (PLK) between the R58 and L59 residues of its propeptide region. Recently, we developed a specific monoclonal antibody to detect the N-terminal side LAP degradation products ending at residue R58 (R58 LAP-DPs) that reflect PLK-dependent TGF-β activation...
October 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30197285/co-delivery-of-a-cd4-t-cell-helper-epitope-via-covalent-liposome-attachment-with-a-surface-arrayed-b-cell-target-antigen-fosters-higher-affinity-antibody-responses
#14
Mostafa A Elbahnasawy, Luke R Donius, Ellis L Reinherz, Mikyung Kim
Liposomal vaccines incorporating adjuvant and CD4 T cell helper peptides enhance antibody responses against weakly immunogenic B cell epitopes such as found in the membrane proximal external region (MPER) of the HIV-1 gp41 subunit. While the inclusion of exogenous helper peptides in vaccine formulations facilitates stronger and more durable antibody responses, the helper peptide incorporation strategy per se may influence the overall magnitude and quality of B cell target antigen immunogenicity. Both variability in individual peptide encapsulation as well as the potential for liposome surface-associated helper peptides to misdirect the humoral response are potential parameters impacting outcome...
October 1, 2018: Vaccine
https://www.readbyqxmd.com/read/30179591/paclitaxel-induced-hmgb1-release-from-macrophages-and-its-implication-for-peripheral-neuropathy-in-mice-evidence-for-a-neuroimmune-crosstalk
#15
Fumiko Sekiguchi, Risa Domoto, Kana Nakashima, Daichi Yamasoba, Hiroki Yamanishi, Maho Tsubota, Hidenori Wake, Masahiro Nishibori, Atsufumi Kawabata
Given our recent evidence for the role of high mobility group box 1 (HMGB1) in chemotherapy-induced peripheral neuropathy (CIPN) in rats, we examined the origin of HMGB1 and the upstream and downstream mechanisms of HMGB1 release involved in paclitaxel-induced neuropathy in mice. Paclitaxel treatment developed mechanical allodynia in mice, as assessed by von Frey test, which was prevented by an anti-HMGB1-neutralizing antibody or thrombomodulin alfa capable of inactivating HMGB1. RAGE or CXCR4 antagonists, ethyl pyruvate or minocycline, known to inhibit HMGB1 release from macrophages, and liposomal clodronate, a macrophage depletor, prevented the paclitaxel-induced allodynia...
October 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30169978/clinical-translation-of-immunoliposomes-for-cancer-therapy-recent-perspectives
#16
Di Wang, Yating Sun, Yange Liu, Fanchao Meng, Robert J Lee
INTRODUCTION: Liposomes have been extensively investigated as drug delivery vehicles. Immunoliposomes (ILs) are antibody-conjugated liposomes designed to selectively target antigen-expressing cells. ILs can be used to deliver drugs to tumor cells for improving efficacy and reducing toxicity. In addition, ILs can be used in immunoassays, immunotherapy, and imaging. Although there has been extensive coverage on ILs in the literature, only a limited number of clinical trials have been reported and no IL drug has been approved by the FDA...
September 2018: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/30165305/igg4-7-responses-correlate-with-contraception-in-mares-vaccinated-with-spayvac
#17
Ursula Bechert, Jennifer Rohde, Heather Freer, Bettina Wagner
SpayVac® is an immunocontraceptive vaccine based on porcine zona pellucida (pZP) antigens and uses a patented liposome formulation (VacciMax™ or DepoVax® ). It has delivered single-dose, long-lasting (4-10 years) immunocontraception in several species. Previous studies have demonstrated a positive correlation between levels of pZP antibodies produced and contraceptive effect; however, individual mares that were consistently infertile did not necessarily have the highest antibody titers. The objective of this study was to identify potential differences in specific immunoglobulin G (IgG) isotype responses among mares treated with SpayVac (VacciMax formulation) to improve our understanding of vaccine efficacy and potential management applications...
November 2018: Theriogenology
https://www.readbyqxmd.com/read/30158286/antitumor-effect-of-nivolumab-on-subsequent-chemotherapy-for-platinum-resistant-ovarian-cancer
#18
Yoshihide Inayama, Junzo Hamanishi, Noriomi Matsumura, Ryusuke Murakami, Kaoru Abiko, Ken Yamaguchi, Tsukasa Baba, Katsuyuki Horie, Ikuo Konishi, Masaki Mandai
Platinum-resistant recurrent ovarian cancer is generally refractory to chemotherapy. Programmed cell death-1 (PD-1) signaling is a new target for antitumor therapy. The anti-PD-1 antibody nivolumab had a 10% durable complete response rate in our phase II clinical trial. However, how nivolumab affects sensitivity to subsequent chemotherapy remains unclear. We encountered several cases of unexpected antitumor response among patients who underwent palliative chemotherapy in the follow-up study of our phase II nivolumab trial (UMIN000005714)...
August 29, 2018: Oncologist
https://www.readbyqxmd.com/read/30142534/a-leishmania-hypothetical-protein-containing-liposome-based-formulation-is-highly-immunogenic-and-induces-protection-against-visceral-leishmaniasis
#19
Patrícia A F Ribeiro, Daniel S Dias, Marcus V M Novais, Daniela P Lage, Grasiele S V Tavares, Débora V C Mendonça, Jamil S Oliveira, Miguel A Chávez-Fumagalli, Bruno M Roatt, Mariana C Duarte, Daniel Menezes-Souza, Fernanda Ludolf, Carlos A P Tavares, Mônica C Oliveira, Eduardo A F Coelho
Leishmania proteins have been evaluated as vaccine candidates against leishmaniasis; however, most antigens present low immunogenicity and need to be added with immune adjuvants. A low number of licensed adjuvants exist on the market today; therefore, research conducted to produce new products is desirable. The present study sought to evaluate the immunogenicity and protective efficacy of a recombinant Leishmania hypothetical protein, namely LiHyR, administered with saponin or liposomes in BALB/c mice. Immunological and parasitological parameters were evaluated, and results showed significant protection against Leishmania infantum infection produced by both compositions in the immunized animals; however, this was not identified when the antigen was used alone...
August 21, 2018: Cytokine
https://www.readbyqxmd.com/read/30138715/anti-polyethylene-glycol-antibodies-alter-the-protein-corona-deposited-on-nanoparticles-and-the-physiological-pathways-regulating-their-fate-in-vivo
#20
Philippe Grenier, Iara Maíra de Oliveira Viana, Eliana Martins Lima, Nicolas Bertrand
Multiple studies highlight the strong prevalence of anti-poly(ethylene glycol) (anti-PEG) antibodies in the general human population. As we develop therapeutic modalities using this polymer, it is increasingly relevant to assess the importance of anti-PEG antibodies on biological performances. Here, we show that the anti-PEG Immunoglobulin M (IgM) raised in mice following the injection of polymeric nanoparticles could have significant neutralizing effects on subsequent doses of PEGylated nanosystems in vivo...
October 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
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