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Galactosylceramide

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https://www.readbyqxmd.com/read/29024788/thermostability-of-the-coating-antigen-and-immunostimulator-in-an-adjuvanted-oral-capsule-vaccine-formulation
#1
Stephanie Longet, Vincenzo Aversa, Daire O'Donnell, Joshua Tobias, Monica Rosa, Jan Holmgren, Ivan S Coulter, Ed C Lavelle
Oral vaccines present an attractive alternative to injectable vaccines for enteric diseases due to ease of delivery and the induction of intestinal immunity at the site of infection. However, susceptibility to gastrointestinal proteolysis, limited transepithelial uptake and a lack of clinically acceptable adjuvants present significant challenges. A further challenge to mass vaccination in developing countries is the very expensive requirement to maintain the cold chain. We recently described the effectiveness of a Single Multiple Pill(®) (SmPill(®)) adjuvanted capsule approach to enhance the effectiveness of a candidate enterotoxigenic Escherichia coli (ETEC) oral vaccine...
October 9, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29018953/frequency-and-proliferative-response-of-circulating-invariant-natural-killer-t-cells-in-pediatric-patients-with-malignant-solid-tumors
#2
Tomoro Hishiki, Naoko Mise, Kazuaki Harada, Fumie Ihara, Mariko Takami, Takeshi Saito, Keita Terui, Mitsuyuki Nakata, Shugo Komatsu, Hideo Yoshida, Shinichiro Motohashi
BACKGROUND: Invariant natural killer T (iNKT) cells play an important role in tumor immunity, enhancing both innate and acquired immunity. We have previously shown the enhancement of antibody-dependent cellular cytotoxicity against neuroblastoma by activated iNKT cells. As a first step towards clinical application, we studied the frequency and proliferative response of circulating iNKT cells in children with and without cancer. METHODS: Blood samples were collected from 10 patients with pediatric malignant solid tumors and 11 patients with non-neoplastic diseases (control)...
October 10, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28947140/co-delivery-of-tumor-derived-exosomes-with-alpha-galactosylceramide-on-dendritic-cell-based-immunotherapy-for-glioblastoma
#3
Hongyu Liu, Ling Chen, Jialin Liu, Hengxing Meng, Rong Zhang, Lin Ma, Liangliang Wu, Songyan Yu, Fei Shi, Ying Li, Lijun Zhang, Lingxiong Wang, Shiyu Feng, Qi Zhang, Yaojun Peng, Qiyan Wu, Chunxi Liu, Xin Chang, Lin Yang, Xinguang Yu, Tianyi Liu
Dendritic cell (DC) vaccine-based immunotherapy for glioblastoma multiforme (GBM) has shown apparent benefit in animal experiments and early-phase clinical trials, but the survival benefit is variable. In this work, we analyzed the mechanism of the potent antitumor immune response induced in vivo by tumor-associated antigen (TAA)-specific DCs with an invariant natural killer T cell (iNKT) adjuvant in orthotopic glioblastoma-bearing rats vaccinated with tumor-derived exosomes and α-galactosylceramide (α-GalCer) -pulsed DCs...
September 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28932640/co-delivery-of-the-nkt-agonist-%C3%AE-galactosylceramide-and-tumor-antigens-to-cross-priming-dendritic-cells-breaks-tolerance-to-self-antigens-and-promotes-antitumor-responses
#4
Reem Ghinnagow, Julie De Meester, Luis Javier Cruz, Caroline Aspord, Stéphanie Corgnac, Elodie Macho-Fernandez, Daphnée Soulard, Josette Fontaine, Laurence Chaperot, Julie Charles, Fabrice Soncin, Fathia Mami-Chouaib, Joel Plumas, Christelle Faveeuw, François Trottein
Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8(+) T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest in the cancer therapy field. In the current study, we have exploited the unique ability of NKT cells to serve as T-helper cells to license dendritic cells (DCs) for cross priming with the aim to generate efficient CTL antitumor responses. To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28915900/a-randomized-phase-ii-study-to-assess-the-effect-of-adjuvant-immunotherapy-using-%C3%AE-galcer-pulsed-dendritic-cells-in-the-patients-with-completely-resected-stage-ii-iiia-non-small-cell-lung-cancer-study-protocol-for-a-randomized-controlled-trial
#5
Hideo Saka, Chiyoe Kitagawa, Yukito Ichinose, Mitsuhiro Takenoyama, Hidenori Ibata, Tatsuo Kato, Koji Takami, Motohiro Yamashita, Tadashi Maeda, Sadanori Takeo, Hitoshi Ueda, Kan Okabayashi, Seiji Nagashima, Tadayuki Oka, Hidenori Kouso, Seiichi Fukuyama, Kentaro Yoshimoto, Mototsugu Shimokawa, Akiko M Saito, Suminobu Ito
BACKGROUND: As the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival. The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II-IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only)...
September 15, 2017: Trials
https://www.readbyqxmd.com/read/28912381/invariant-natural-killer-t-cells-promote-immunogenic-maturation-of-lung-dendritic-cells-in-mouse-models-of-asthma
#6
Qing He, Linlin Liu, Qiaoyu Yang, Ailing Wang, Shuo Chen, Ruiyun Li, Yi Huang, Guqin Zhang, Xuhong Ding, Hongying Yu, Suping Hu, Hanxiang Nie
Our previous study showed that invariant natural killer T (iNKT) cells might act as an adjuvant to promote Th2 inflammatory responses in an OVA-induced mouse model of allergic asthma, but the mechanism remains unknown. To clarify the underlying mechanism through which iNKT cells promote Th2 inflammatory responses, we investigated the modulatory influence of iNKT cells on phenotypic and functional maturation of lung dendritic cells (LDCs) using iNKT cell-knockout mice, specific iNKT cell activation, co-culture experiments, and adoptive transfer of iNKT cells in mouse models of asthma...
September 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28892129/invariant-natural-killer-t-cell-development-and-function-with-loss-of-microrna-155
#7
Adolfo B Frias, Heather M Buechel, Arpan Neupane, Louise M D'Cruz
Invariant natural killer T (iNKT) cells are adaptive T cells with innate-like characteristics including rapid cytokine production and a proliferative response to stimulation. Development of these cells in the thymus is dependent on expression of the microRNA (miRNA) processing enzyme Dicer, indicating that iNKT cells probably have distinct miRNA requirements for gene regulation during development. The miRNA miR-155 has previously been shown to have numerous roles in T cells, including regulation of proliferation and differentiation, and positive modulation of interferon-γ expression...
September 11, 2017: Immunology
https://www.readbyqxmd.com/read/28874416/growth-differentiation-factor-15-mediates-systemic-glucose-regulatory-action-of-t-helper-type-2-cytokines
#8
Seong Eun Lee, Seul Gi Kang, Min Jeong Choi, Saet-Byel Jung, Min Jeong Ryu, Hyo Kyun Chung, Joon Young Chang, Yong Kyung Kim, Ju Hee Lee, Koon Soon Kim, Hyun Jin Kim, Heung Kyu Lee, Hyon-Seung Yi, Minho Shong
Th2 cytokines, including IL-13 and IL-4, produced in adipose tissue are critical regulators of intra-adipose and systemic lipid and glucose metabolism. Furthermore, IL-13 is a potential therapy for insulin resistance in obese mouse models. Here, we examined mediators produced by adipocytes that are responsible for regulating systemic glucose homeostasis in response to Th2 cytokines. We used RNA-seq data analysis of cultured adipocytes to screen factors secreted in response to recombinant IL-13. Recombinant IL-13 induced expression of growth differentiation factor 15 (GDF15) via the Janus kinase-activated STAT6 pathway...
September 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28872688/liposomal-%C3%AE-galactosylceramide-is-taken-up-by-gut-associated-lymphoid-tissue-and-stimulates-local-and-systemic-immune-responses
#9
Kan Kaneko, Arlene McDowell, Yasuyuki Ishii, Sarah Hook
OBJECTIVES: α-Galactosylceramide (α-GalCer), a synthetic glycosphingolipid that exhibits potent immunostimulatory effects through activation of natural killer T (NKT) cells, can be used to treat conditions such as atopy, cancer, infection and autoimmunity. Administration of therapeutics through the oral route has advantages such as patient convenience, safety and reduced cost; however, there has been little research to investigate whether oral delivery of α-GalCer is possible. The aim of this study was therefore to determine whether α-GalCer formulated in either DMSO/Tween 80 or in liposomes, could access lymphoid tissue and stimulate immune activation following oral administration...
September 5, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28860937/a-brief-review-of-clinical-trials-involving-manipulation-of-invariant-nkt-cells-as-a-promising-approach-in-future-cancer-therapies
#10
REVIEW
Małgorzata Waldowska, Agnieszka Bojarska-Junak, Jacek Roliński
In the recent years researchers have put a lot of emphasis on the possible immunotherapeutic strategies able to target tumors. Many studies have proven that the key role in recognition and eradication of cancer cells, both for mice and humans, is being conducted by the invariant natural killer T-cells (NKT). This small subpopulation of lymphocytes can kill other cells, either directly or indirectly, through the natural killer cells' (NK) activation. They can also swiftly release cytokines, causing the involvement of elements of the innate and acquired immune system...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28826286/characterization-and-evaluation-of-stabilized-particulate-formulations-as-therapeutic-oral-vaccines-for-allergy
#11
Kan Kaneko, Arlene McDowell, Yasuyuki Ishii, Sarah Hook
Allergic conditions affect more than a quarter of the population in developed countries, but currently available treatments focus more on symptom relief than treating the underlying atopic condition. α-galactosylceramide (α-GalCer) is a potent immunomodulating compound that has been shown to have a regulatory effect when delivered systemically in nanoparticles. Parenteral delivery is not preferred for chronic conditions such as allergy, therefore the aim of this study was to determine if a regulatory response could be induced through oral administration in a model of atopy through incorporation of α-GalCer into stable particulate formulations (cationic liposomes, polymerized liposomes and poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs))...
August 21, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28780376/retinoic-acid-induction-of-cd1d-expression-primes-chronic-lymphocytic-leukemia-b-cells-for-killing-by-cd8-invariant-natural-killer-t-cells
#12
Yasmeen G Ghnewa, Vincent P O'Reilly, Elisabeth Vandenberghe, Paul V Browne, Anthony M McElligott, Derek G Doherty
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5...
August 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28743554/solubilization-of-%C3%AE-galactosylceramide-in-aqueous-medium-impact-on-natural-killer-t-cell-activation-and-antitumor-responses
#13
Elodie Macho-Fernandez, Neila Chekkat, Christophe Ehret, Jean-Sébastien Thomann, Marcella De Giorgi, Maria Vittoria Spanedda, Line Bourel-Bonnet, Didier Betbeder, Béatrice Heurtault, Christelle Faveeuw, Sylvie Fournel, Benoît Frisch, François Trottein
The potent antitumor effect of α-galactosylceramide (α-GalCer) is based on its recognition by invariant Natural Killer T cells (iNKT) after its capture and presentation by antigen presenting cells including dendritic cells (DCs). Synthetic α-GalCer has already been tested in advanced cancer patients but no or only moderate clinical responses were obtained. To optimize α-GalCer efficacy, we have postulated that alternative formulations impacting its molecular organization in aqueous medium could modify DC uptake and iNKT-based immune responses...
July 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28714776/tissue-localization-of-glycosphingolipid-accumulation-in-a-gaucher-disease-mouse-brain-by-lc-esi-ms-ms-and-high-resolution-maldi-imaging-mass-spectrometry
#14
E Ellen Jones, Wujuan Zhang, Xueheng Zhao, Cristine Quiason, Stephanie Dale, Sheerin Shahidi-Latham, Gregory A Grabowski, Kenneth D R Setchell, Richard R Drake, Ying Sun
To better understand regional brain glycosphingolipid (GSL) accumulation in Gaucher disease (GD) and its relationship to neuropathology, a feasibility study using mass spectrometry and immunohistochemistry was conducted using brains derived from a GD mouse model (4L/PS/NA) homozygous for a mutant GCase (V394L [4L]) and expressing a prosaposin hypomorphic (PS-NA) transgene. Whole brains from GD and control animals were collected using one hemisphere for MALDI FTICR IMS analysis and the other for quantitation by LC-ESI-MS/MS...
July 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28694168/characterizing-porcine-invariant-natural-killer-t-cells-a-comparative-study-with-nk-cells-and-t-cells
#15
Guan Yang, Bianca L Artiaga, Sarah T Lewis, John P Driver
CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T cells that share phenotypic characteristics of both NK and conventional T cells (Tconv). Although iNKT cells have been well characterized in mice and humans, functional CD1d and CD1d-restricted iNKT cells are not universally expressed in mammals. Swine express iNKT cells that can be detected using α-galactosylceramide (α-GalCer)-loaded CD1d tetramers. In the present study, we characterized iNKT cells from the blood, spleen, lymph node, lung and liver of commercial mixed-breed pigs, and compared their phenotype to NK cells and Tconv...
July 8, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28674535/leishmania-infantum-exoproducts-inhibit-human-invariant-nkt-cell-expansion-and-activation
#16
Renata Belo, Nuno Santarém, Cátia Pereira, Begoña Pérez-Cabezas, Fátima Macedo, Maria Leite-de-Moraes, Anabela Cordeiro-da-Silva
Leishmania infantum is one of the major parasite species associated with visceral leishmaniasis, a severe form of the disease that can become lethal if untreated. This obligate intracellular parasite has developed diverse strategies to escape the host immune response, such as exoproducts (Exo) carrying a wide range of molecules, including parasite virulence factors, which are potentially implicated in early stages of infection. Herein, we report that L. infantum Exo and its two fractions composed of extracellular vesicles (EVs) and vesicle-depleted-exoproducts (VDEs) inhibit human peripheral blood invariant natural killer T (iNKT) cell expansion in response to their specific ligand, the glycolipid α-GalactosylCeramide (α-GalCer), as well as their capacity to promptly produce IL-4 and IFNγ...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28660574/high-performance-chromatographic-separation-of-cerebrosides
#17
Renaud Sicard, Ralf Landgraf
High-performance thin-layer chromatography (HPTLC) is a very robust, fast, and inexpensive technique that enables separation of complex mixtures. Here, we describe the analytical separation of glucosylceramide and galactosylceramide by HPTLC. This technique can be used for quantitation purposes but also with small modification for subsequent mass spectrum analyses for structural determination.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28655912/galactosylsphingamides-new-%C3%AE-galcer-analogues-to-probe-the-f-pocket-of-cd1d
#18
Joren Guillaume, Jing Wang, Jonas Janssens, Soumya G Remesh, Martijn D P Risseeuw, Tine Decruy, Mathy Froeyen, Dirk Elewaut, Dirk M Zajonc, Serge Van Calenbergh
Invariant Natural Killer T-cells (iNKT-cells) are an attractive target for immune response modulation, as upon CD1d-mediated stimulation with KRN7000, a synthetic α-galactosylceramide, they produce a vast amount of cytokines. Here we present a synthesis that allows swift modification of the phytosphingosine side chain by amidation of an advanced methyl ester precursor. The resulting KRN7000 derivatives, termed α-galactosylsphingamides, were evaluated for their capacity to stimulate iNKT-cells. While introduction of the amide-motif in the phytosphingosine chain is tolerated for CD1d binding and TCR recognition, the studied α-galactosylsphingamides showed compromised antigenic properties...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645718/optimizing-adjuvants-for-intradermal-delivery-of-menc-glycoconjugate-vaccine
#19
Agnese Donadei, Cristiana Balocchi, Maria R Romano, Luigi Panza, Roberto Adamo, Francesco Berti, Derek T O'Hagan, Simona Gallorini, Barbara C Baudner
Intradermal vaccine delivery is a promising alternative to the conventional intramuscular route. The skin layer is immunologically supported by a densely network of antigen presenting cells, while the skeletal muscle is loaded with a relatively sparse population of APCs. Nevertheless, the vaccine to be suitable for intradermal delivery needs a new formulation to facilitate either smaller injection volumes or the introduction into new delivery devises as micro-needles. This study presents a proof of concept for intradermal delivery of the MenC-CRM197 glycoconjugate vaccine using a mouse model...
July 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28633979/zerumbone-modulates-cd1d-expression-and-lipid-antigen-presentation-pathway-in-breast-cancer-cells
#20
Ritis K Shyanti, Anuradha Sehrawat, Shivendra V Singh, J P N Mishra, Rana P Singh
Natural Killer T (NKT) cells based cancer immunotherapy is an evolving area of cancer therapy, but tumors escape from this treatment modality by altering CD1d expression and its antigen presentation pathway. Here, we have studied the relation of CD1d expression in various breast cancer cell lines to their viability and progression. We observed a novel phenomenon that CD1d expression level increases with the progressive stage of the cancer. A small molecule, zerumbone (ZER) caused down-regulation of CD1d that was accompanied by breast cancer cell growth in vitro...
October 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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