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Galactosylceramide

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https://www.readbyqxmd.com/read/29210987/prophylactic-sublingual-immunization-with-mycobacterium-tuberculosis-subunit-vaccine-incorporating-the-natural-killer-t-cell-agonist-alpha-galactosylceramide-enhances-protective-immunity-to-limit-pulmonary-and-extra-pulmonary-bacterial-burden-in-mice
#1
Arshad Khan, Shailbala Singh, Gloria Galvan, Chinnaswamy Jagannath, K Jagannadha Sastry
Infection by Mycobacterium tuberculosis (Mtb) remains a major global concern and the available Bacillus Calmette-Guerin (BCG) vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer), a potent natural killer T (NKT) cell agonist...
December 6, 2017: Vaccines
https://www.readbyqxmd.com/read/29202455/a-simple-clinically-relevant-therapeutic-vaccine-shows-long-term-protection-in-an-aggressive-delayed-treatment-b-lymphoma-model
#2
Pallab Pradhan, Jardin Leleux, Jiaying Liu, Krishnendu Roy
Despite initial remission after successful treatments, B lymphoma patients often encounter relapses and resistance causing high mortality. Thus, there is a need to develop therapies that prevent relapse by providing long-term protection and, ultimately, lead to functional cure. In this study, our goal was to develop a simple, clinically relevant, and easily translatable therapeutic vaccine that provides durable immune protection against aggressive B cell lymphoma and identify critical immune biomarkers that are predictive of long-term survival...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29199207/effects-of-plant-sphingolipids-on-inflammatory-stress-in-differentiated-caco-2-cells
#3
Shinji Yamashita, Takuya Seino, Kazuhiko Aida, Mikio Kinoshita
To determine the mechanism underlying the anti-inflammatory effects of plant sphingolipids, especially plant glucosylceramide (GlcCer), the effects of plant sphingolipids on inflammatory stress in differentiated Caco-2 cells were compared to those of a sphingolipid of animal origin, galactosylceramide (GalCer). Addition of GlcCer or GalCer suppressed cell injury caused lipopolysaccharide (LPS)- and TNF-α-induced inflammatory stress and induction of apoptosis in differentiated Caco-2 cells. There was no difference in the suppressive effect between GlcCer and GalCer...
2017: Journal of Oleo Science
https://www.readbyqxmd.com/read/29183709/unappreciated-diversity-within-the-pool-of-cd1d-restricted-t-cells
#4
REVIEW
Daniel G Pellicci, Adam P Uldrich
Studies of lipid reactive CD1d-restricted T cells have focussed on α-galactosylceramide reactive semi-invariant Type I NKT cells, which influence a broad range of immune responses. Much less is known about other CD1d-restricted T cells with respect to TCR diversity, function, the types of antigens they recognize and how they specifically recognize antigens presented by CD1d. In this review, we reflect on recent literature that highlights unexpected complexity within the pool of CD1d-restricted T cells and emphasize how TCR diversity greatly broadens the scope of antigen recognition...
November 25, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29163493/alpha-galactosylceramide-cd1d-antibody-fusion-proteins-redirect-invariant-natural-killer-t-cell-immunity-to-solid-tumors-and-promote-prolonged-therapeutic-responses
#5
REVIEW
Lianjun Zhang, Alena Donda
Major progress in cancer immunotherapies have been obtained by the use of tumor targeting strategies, in particular with the development of bi-functional fusion proteins such as ImmTacs or BiTes, which engage effector T cells for targeted elimination of tumor cells. Given the significance of invariant natural killer T (iNKT) cells in bridging innate and adaptive immunity, we have developed a bi-functional protein composed of the extracellular part of CD1d molecule that was genetically fused to an scFv fragment from high affinity antibodies against HER2 or CEA...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163480/differentiation-of-il-17-producing-invariant-natural-killer-t-cells-requires-expression-of-the-transcription-factor-c-maf
#6
Jhang-Sian Yu, Michito Hamada, Shigeo Ohtsuka, Keigyou Yoh, Satoru Takahashi, Shi-Chuen Miaw
c-Maf belongs to the large Maf family of transcription factors and plays a key role in the regulation of cytokine production and differentiation of TH2, TH17, TFH, and Tr1 cells. Invariant natural killer T (iNKT) cells can rapidly produce large quantity of TH-related cytokines such as IFN-γ, IL-4, and IL-17A upon stimulation by glycolipid antigens, such as α-galactosylceramide (α-GalCer). However, the role of c-Maf in iNKT cells and iNKT cells-mediated diseases remains poorly understood. In this study, we demonstrate that α-GalCer-stimulated iNKT cells express c-Maf transcript and protein...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29098499/functional-role-of-natural-killer-t-cells-in-non-obese-pre-diabetes-model-mice
#7
Mikako Saito, Misako Kaburagi, Keiko Otokuni, Genu Takahashi
Pre-diabetic patients have a high risk of developing diabetes as well as other associated diseases. From the viewpoint of risk assessment and to assist the development of protective therapies, we focused on the functional role of natural killer T (NKT) cells in pre-diabetes. We found that the expression of an NKT cell marker gene, Va14-Ja18, was significantly lower in specific tissues/organs such as adipose tissue and pancreas in non-obese pre-diabetes model mice than in their normal littermates. Subsequently, in the pre-diabetes model mice, Va14-Ja18 was activated with α-galactosylceramide (α-GalCer) and its effect on glucose tolerance was estimated...
November 2, 2017: Cytotechnology
https://www.readbyqxmd.com/read/29094183/a-phase-i-vaccination-study-with-dendritic-cells-loaded-with-ny-eso-1-and-%C3%AE-galactosylceramide-induction-of-polyfunctional-t-cells-in-high-risk-melanoma-patients
#8
Olivier Gasser, Katrina J Sharples, Catherine Barrow, Geoffrey M Williams, Evelyn Bauer, Catherine E Wood, Brigitta Mester, Marina Dzhelali, Graham Caygill, Jeremy Jones, Colin M Hayman, Victoria A Hinder, Jerome Macapagal, Monica McCusker, Robert Weinkove, Gavin F Painter, Margaret A Brimble, Michael P Findlay, P Rod Dunbar, Ian F Hermans
Vaccines that elicit targeted tumor antigen-specific T-cell responses have the potential to be used as adjuvant therapy in patients with high risk of relapse. However, the responses induced by vaccines in cancer patients have generally been disappointing. To improve vaccine function, we investigated the possibility of exploiting the immunostimulatory capacity of type 1 Natural killer T (NKT) cells, a cell type enriched in lymphoid tissues that can trigger improved antigen-presenting function in dendritic cells (DCs)...
November 1, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29054890/natural-killer-t-cell-immunotherapy-in-combination-with-chemotherapy-induced-immunogenic-cell-death-targets-metastatic-breast-cancer
#9
Simon Gebremeskel, Lynnea Lobert, Kaitlyn Tanner, Brynn Walker, Tora Oliphant, Livia E Clarke, Graham Dellaire, Brent Johnston
Natural killer T (NKT) cells are glycolipid-reactive lymphocytes that promote cancer control. In previous studies, NKT-cell activation improved survival and antitumor immunity in a post-surgical mouse model of metastatic breast cancer. Herein, we investigated whether NKT-cell activation could be combined with chemotherapeutic agents to augment therapeutic outcomes. Gemcitabine and cyclophosphamide analogs enhanced the potential immunogenicity of 4T1 mammary carcinoma cells by increasing the expression of antigen-presenting molecules (MHC-I, MHC-II, and CD1d) and promoting exposure or release of immunogenic cell death markers (calreticulin, HMGB1 and ATP)...
October 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29043774/augmenting-influenza-specific-t-cell-memory-generation-with-a-natural-killer-t-cell-dependent-glycolipid-peptide-vaccine
#10
Regan J Anderson, Jasmine Li, Lukasz Kedzierski, Benjamin J Compton, Colin M Hayman, Taryn L Osmond, Ching-Wen Tang, Kathryn J Farrand, Hui-Fern Koay, Catarina Filipa Dos Santos Sa E Almeida, Lauren R Holz, Geoffrey M Williams, Margaret A Brimble, Zhongfang Wang, Marios Koutsakos, Katherine Kedzierska, Dale I Godfrey, Ian F Hermans, Stephen J Turner, Gavin F Painter
The development of a universal vaccine for influenza A virus (IAV) that does not require seasonal modification is a long-standing health goal, particularly in the context of the increasing threat of new global pandemics. Vaccines that specifically induce T cell responses are of considerable interest because they can target viral proteins that are more likely to be shared between different virus strains and subtypes and hence provide effective cross-reactive IAV immunity. From a practical perspective, such vaccines should induce T cell responses with long-lasting memory, while also being simple to manufacture and cost-effective...
November 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29024788/thermostability-of-the-coating-antigen-and-immunostimulator-in-an-adjuvanted-oral-capsule-vaccine-formulation
#11
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
#12
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
#13
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, Yasushi Uemura, 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 (iNKT) cell 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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