57 results about "Galactosyl ceramide" patented technology

Methods for synthesis and preparation of alpha-glycosphingolipids are provided. Methods for synthesis of α-galactosyl ceramide, and pharmaceutically active analogs and variants thereof are provided. Novel alpha-glycosphingolipids are provided, wherein the compounds are immunogenic compounds which serve as ligands for NKT (natural killer T) cells.

This invention relates to the in vivo expansion of NKT cells by their exposure to mature dendritic cells expressing α-galactosyl ceramide and to methods of use thereof in modulating immune responses, such as anti-cancer responses, and enhancing memory responses.

α-Galactosylceramides and glycosylceramides (“ceramide-like glycolipids”) that modulate NK T cells. The ceramide-like glycolipids vary in the cytokines induced in NK T cells and vary in the antigen-presenting cells that are capable of efficiently presenting the compounds to NK T cells. Pharmaceutical compositions of the ceramide-like glycolipids are provided, as are pharmaceutical compositions of the ceramide-like glycolipids combined with dendritic cells. Methods utilizing the ceramide-like glycolipids in vaccines, to activate NK T cells, to stimulate the immune system, and to treat mammals are also provided. The invention also provides methods of evaluating a compound for its ability to activate an NK T cell in the presence of a cell expressing a CD1d protein.

Provided are an iPS cell derived from a somatic cell such as an NKT cell, having the α-chain region of the T cell antigen receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, NKT cells differentiated from the iPS cell, a method of creating the same, and an immune cell therapy agent prepared using cells differentiated from the iPS cell. Also provided are an iPS cell having TCRα rearranged to NKT-TCR (NKT-iPS cell), obtained by contacting a somatic cell, such as an NKT cell, having the α-chain region of the T cell antigen receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, with nuclear reprogramming factors, isolated NKT cells obtained by differentiating the iPS cell ex vivo (iPS-NKT cell), a method of generating CD4 / CD8-double positive NKT cells (DP-NKT cells) and mature NKT cells from NKT-iPS cells by altering the combination of feeder cells and / or cytokines, a method of expanding the iPS-NKT cells, and an NKT cell cytotherapy agent comprising NKT cells activated with α-galactosyl ceramide (α-GalCer), or iPS-NKT cells, and α-GalCer in combination.

Immunogenic compositions, cancer vaccines and methods for treating cancer are provided. Compositions comprising: (a) a glycan such as Globo H or an immunogenic fragment thereof, wherein the glycan is conjugated with a carrier protein by a linker such as para-nitrophenyl; and (b) an adjuvant comprising glycolipid capable of binding CDId on a dendritic cell, such as an a-galactosyl-ceramide derivative, wherein the immunogenic composition induces an immune response that induces a higher relative level of IgG isotype antibodies as compared to IgM isotype antibodies, are provided. Immunogenic compositions comprising the carrier protein diphtheria toxin cross-reacting material 197 (DT-CRM 197) and the adjuvant C34 are provided. Antibodies generated by immunogenic compositions disclosed herein further neutralize at least one of the antigens Globo H, stage-specific embryonic antigen-3 (SSEA-3) and stage-specific embryonic antigen-4 (SSEA-4). Therapeutics against breast cancer stem cells comprising immunogenic compositions comprising Globo H, SSEA-3 or SSEA-4 conjugated with DT-CRM 197.

There are disclosed compound of formula I, in which R1 represents a hydrophobic moiety adapted to occupy the C′ channel of human CDId, R2 represents a hydrophobic moiety adapted to occupy the A′ channel of human CDId, such that R1 fills at least at least 30% of the occupied volume of the C′ channel compared to the volume occupied by the terminal nC14H29 of the sphingosine chain of α-galactosylceramide when bound to human CDId and R2 fills at least 30% of the occupied volume of the A′ channel compared to the volume occupied by the terminal nC25H51 of the acyl chain of α-galactosylceramide when bound to human CDId R3 represents hydrogen or OH, Ra and Rb each represent hydrogen and in addition, when R3 represents hydrogen, Ra and Rb together may form a single bond, X represents or —CHA(CHOH)nY or —P(═0)(0−)0CH2(CH0H)mY, in which Y represents CHB1B2, n represents an integer from 1 to 4, m represents 0 or 1, A årepresents hydrogen, one of B1 and B2 represents H, OH or phenyl, and the other represents hydrogen or one of B1 and B2 represents hydroxyl and the other represents phenyl, in addition, when n represents 4, then A together with one of B1 and B2 together forms a single bond and the other of B1 and B2 represents H, OH or OSO3H and pharmaceutically acceptable salts thereof; the compounds of formula I are indicted for use in the treatment of a virus, microbial infection, parasite, an autoimmune disease, cancer, allergy or asthma

The invention relates to a compound immunopotentiator and an application in preparation of veterinary vaccines. The compound immunopotentiator contains 0.5-100 microgram / mL of nucleic acid sequence with a CpG motif, 0.5-1000 microgram / mL of alpha-galactosyl ceramide, 5-2000 microgram / mL of beta-glucan, and 5-2000 microgram / mL of levomisole, wherein the nucleic acid sequence with a CpG motif is shown in SEQ ID NO.1. When the compound immunopotentiator of the invention is mixed with an H9-subtype avian influenza inactivated vaccine, the immune window period is shortened by 2 weeks; the antibody persistent period is prolonged by 8 weeks; sterilizing immunity protection is provided for H9-subtype homotype strain attack; and the antigen content for preparing vaccines is reduced.

The invention relates to the use of β-glycolipids as immunomodulators. More particularly, the invention relates to the use of β-glycolipids, preferably, β-lactosyl-ceramide, β-glucosylceramide, β-galactosyl-ceramide, ceramid and β-lactosyl-ceramide, as well as any mixture or combination thereof for the treatment of immune related disorders. The present invention further relates to a process for the modulation of the Th1 / Th2 cell balance toward anti-inflammatory cytokine producing cells, in a subject suffering from an immune related disorder. Therapeutic compositions and method for the preparation of these compositions are also provided.

Provided are an iPS cell derived from a somatic cell such as an NKT cell, having the α-chain region of the T cell antigen receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, NKT cells differentiated from the iPS cell, a method of creating the same, and an immune cell therapy agent prepared using cells differentiated from the iPS cell. Also provided are an iPS cell having TCRα rearranged to NKT-TCR (NKT-iPS cell), obtained by contacting a somatic cell, such as an NKT cell, having the α-chain region of the T cell antigen receptor gene rearranged to uniform Vα-Jα in an NKT cell receptor-specific way, with nuclear reprogramming factors, isolated NKT cells obtained by differentiating the iPS cell ex vivo (iPS-NKT cell), a method of generating CD4 / CD8-double positive NKT cells (DP-NKT cells) and mature NKT cells from NKT-iPS cells by altering the combination of feeder cells and / or cytokines, a method of expanding the iPS-NKT cells, and an NKT cell cytotherapy agent comprising NKT cells activated with α-galactosyl ceramide (α-GalCer), or iPS-NKT cells, and α-GalCer in combination.

The invention provides an alpha-galactosyl ceramide new isomer and its synthetic method. Configuration of sphingosine chain is changed to 4,5-cis double bond sphingosine chain. According to the invention, reaction steps are shortened, yield is raised, and aftertreatment and purification steps are omitted. The synthetic method can be used for total synthesis of similar glycosyl ceramide and satisfies wide range of development, research and application of different glycosyl ceramide.

The invention belongs to the technical field of immune cell in-vitro culture, and particularly discloses a culture method of umbilical cord blood lymphocyte CIK. The method comprises the following steps: by using umbilical cord blood as a treatment object, separating the umbilical cord blood mononuclear cells, purifying and inducing the CIK cells, culturing and amplifying the CIK cells, and finally, centrifuging to collect the mature umbilical cord blood CIK cells, thereby obtaining the product. The IFN-gamma and alpha-galactose ceramide are added to activate the CIK cells, and CD3 monoclonalantibodies, IL-1 alpha, IL-2 and IL-1 beta are added in the early culture stage to perform continuous stimulation, thereby saving the coating time and enhancing the activation efficiency and amplification efficiency of effector cell groups.

The invention provides a biomarker for diagnosing cerebral infarction and white matter lesion and application of the biomarker. The biomarker is an application of galactosylceramide in preparation of a detection reagent for diagnosing cerebral infarction and white matter lesions, and the biomarker galactosylceramide is combined with glucosylceramide, beta-allopietapentaol, platyclalene, 1, 3Z, 6Z, 9Z-nonane tetraene, p-cymene, oxalic acid, 3-(stearoyloxy)-4-(trimethyl ammonium) butyrate for diagnosing cerebral infarction and white matter lesions, so the risk of suffering from cerebral infarction and white matter lesion can be judged, and the cerebral infarction and white matter lesion can be prevented in advance.

Adjuvant combinations comprising at least one NKT activator, such as alpha-galactosylceramide (α-Gal-Cer) or iGb3, a CD40 agonist and optionally an antigen are disclosed. The use of these immune adjuvants for treatment of various chronic diseases such as cancers is also provided.

Methods for synthesis and preparation of alpha-glycosphingolipids are provided. Methods for synthesis of α-galactosyl ceramide, and pharmaceutically active analogs and variants thereof are provided. Novel alpha-glycosphingolipids are provided, wherein the compounds are immunogenic compounds which serve as ligands for NKT (natural killer T) cells.

The invention relates to a ceramide preparation pure dry powder which is white without peculiar smell and is made from galactosyl ceramide, phosphatide and cholesterol which are mixed uniformly. The weights of the galactosyl ceramide, the phosphatide and the cholesterol respectively take 60 percent to 70 percent, 20 percent to 25 percent and 10 percent to 15 percent in the total weight of the dry powder. A dry pasty ceramide preparation developed by East China Normal University and ethanol are used as raw material and extracting solution respectively. The ethanol is used for extracting ceramide from the dry pasty ceramide preparation twice, the extract is frozen and dried, and the dry powder is prepared. The dry powder is used as the raw material; a small quantity of 95 percent medical ethanol is added to be heated and dissolved and injected into hot stirred distilled water by an injector; and ceramide lipidosome emulsion is prepared. The dry powder is added into cosmetic; the addition is 0.01 percent to 0.1 percent of the weight of the cosmetic; the dry powder and the cosmetic are stirred uniformly; and the cosmetic with moisturizing function is prepared.

A liposome containing a regulatory cell ligand such as α-galactosyl ceramide or β-galactosyl ceramide is employed as the active ingredient of a drug for preventing or treating immune diseases etc.

The invention discloses an SOD (superoxide dismutase) ethosome and a preparation method thereof. The ethosome mainly consists of the following components: galactosyl ceramide, PEG (polyethylene glycol) modified SOD, low-molecule alcohol and water; and the preparation method mainly comprises the following steps: according to constituting proportions of the components, dissolving the galactosyl ceramide in a low-molecule alcohol mixed solution so as to obtain a solution A; dissolving the PEG modified SOD in ethanol and uniformly stirring so as to obtain a solution B; mixing the solution A with the solution B; adding a buffer solution as a uniform milk white suspension is formed; then, ultrasonically processing in an ice-bath condition; and finally, processing by virtue of a filtering membrane, so that the SOD ethosome is obtained. The SOD ethosome has the advantages of strong stability, strong transdermal penetration and simple preparation process.

The invention provides biomarkers for diagnosing cerebral infarction and white matter lesions and applications thereof. The biomarker is the application of galactosylceramide in the preparation of detection reagents for diagnosing cerebral infarction and white matter lesions. The biomarkers Galactosylceramide combined with glucosylceramide, β‑alpipentol, arborvitene, 1,3Z,6Z,9Z‑nonanetetraene, p-cymene, oxalic acid, 3‑(stearyloxy) ‑4‑(Trimethylammonium) butyrate can be used to judge the risk of cerebral infarction and white matter lesions, and can prevent and prevent cerebral infarction and white matter lesions in advance.

The present invention relates to a method for screening a modulator of a TMEM16 family member, which comprises the following steps:(1) treating cells expressing the TMEM16 family member with a candidate of the modulator, and(2) determining whether the candidate alters distribution of a lipid selected from phosphatidylserine, phosphatidylcholine, and galactosylceramide in plasma membrane of the cells,wherein a candidate which increases distribution of phosphatidylserine in the outer leaflet of plasma membrane compared to control is selected as a modulator enhancing a function of the TMEM16 family member, and a candidate which decreases distribution of phosphatidylserine in the outer leaflet of plasma membrane compared to control is selected as a modulator suppressing a function of the TMEM16 family member, anda candidate which increases distribution of phosphatidylcholine or galactosylceramide in the inner leaflet of plasma membrane compared to control is selected as a modulator enhancing a function of the TMEM16 family member, and a candidate which decreases distribution of phosphatidylcholine or galactosylceramide in the inner leaflet of plasma membrane compared to control is selected as a modulator suppressing a function of the TMEM16 family member.

The invention relates to a method of preparation of alpha-galactosyl ceramides compounds of formula (I) comprising a step a) of glycosylation of a compound of formula (II) with a compound of formula (III).

The invention provides analogs of alpha-galactosyl ceramide that increase the immune response elicited by various antigens. It also provides methods of using such compounds to increase the effectiveness of vaccines.

The present invention relates to an immunoprophylactic and therapeutic vaccine comprising a peripheral blood mononuclear cell loaded with a natural killer T cell ligand and an antigen, and more particularly, to an immunotherapeutic vaccine comprising a peripheral blood mononuclear cell loaded with alpha-galactosylceramide, a natural killer T cell ligand and a glycolipid. The compositions of the present invention are readily available because there is no need to isolate specific cells from peripheral blood mononuclear cells. Besides, the immunization of the peripheral blood mononuclear cells loaded with the natural killer T cell ligands and antigens not only induces the obvious-level activation of the natural killer cells and the natural killer T cells and the response of cytotoxic T lymphocytes, but also has a synergistic treatment effect in the aspect of treating malignant tumors. Therefore, the compound can be beneficially used as an anti-cancer immunotherapeutic agent.

The invention provides a biomarker for white matter lesion and application thereof, and particularly relates to application of a biomarker ceramide (d18: 0 / 24: 1 (15Z)) in preparation of a detection reagent for diagnosing white matter lesion. The risk of the white matter lesion is judged by combining a biomarker lipoceramide (d18: 0 / 24: 1 (15Z)) with one or two of PEIPC, phosphatidylcholine (P-18: 1 (9Z) / 0: 0), phosphatidylcholine (O-18: 0 / 0: 0) or galactosylceramide (d18: 0 / 16: 0), and the white matter lesion can be prevented in advance.

A method for the production of a-O-galactosyl ceramide precursor is demonstrated. The method involves the reaction of galactosyl iodide with a sphingosine derivative or phytosphingosine derivative in the presence of a quaternary ammonium iodide salt to prepare the a-O-galactosyl ceramide precursor in the a-anomer form. The a-O-galactosyl ceramide is then prepared by reaction with a suitable fatty acid or fatty acid derivative.

This invention relates to the in vivo expansion of NKT cells by their exposure to mature dendritic cells expressing α-galactosyl ceramide and to methods of use thereof in modulating immune responses, such as anti-cancer responses, and enhancing memory responses.

The invention belongs to the technical field of gene engineering, and particularly relates to a genetically engineered bacterium of galactosylceramide as well as a construction method and application of the genetically engineered bacterium of galactosylceramide. On the basis of an existing delta pyrG aspergillus oryzae auxotroph strain, the metabolic flux of neutral glycosphingolipid is enhanced through overexpression of an AoCerS gene; meanwhile, the expression of a neutral sphingolipid glucosylceramide (GlcCers) synthetase gene AoUGCG is inhibited, so that the common intermediate metabolite flux of the GlcCers and galactosylceramide (GalCers) flows to the synthesis of the GalCers. The GalCers relative content of the constructed aspergillus oryzae engineering strain is increased by more than two times compared with that of a control strain, and is increased by about 70% compared with that of the control strain.

To provide a natural killer T cell (NKT cell) therapy that does not need activation with α-galactosyl ceramide (Gal-Cer).SOLUTION: Provided herein are CIK NKT cells that can be activated in the absence of Gal-Cer. In some embodiments, more than 50% of the cells in the CIK NKT cell population express CD56 and CD3, and less than 10% of the cells in the population express Va24. Also provided are compositions and kits comprising a plurality of CIK NKT cells from the population. Methods of producing the CIK NKT cells and methods of using the cells to treat cancer are also provided.SELECTED DRAWING: Figure 2

The invention discloses an NK cell culture solution and a culture method thereof. The culture solution comprises an amplification culture solution and an induction activation culture solution, wherein the amplification culture solution is based on a serum-free culture medium and is added with cell factors such as IL-2, IL-12, IL-15 and IL-18, and the induction activation culture solution is based on the amplification culture solution and is added with induction activation factors such as OK432, CD16-alpha, a pseudomonas aeruginosa injection, alpha-galactosylceramide and CD137L. The induction activation factor CD16-alpha added in the NK cell culture fluid can activate NK cells independently or in combination with OK432, a pseudomonas aeruginosa injection, alpha-galactosylceramide and the like, so that the NK cells grow quickly, and the CD3-C56 + ratio of the NK cells can be increased; after the CD16-alpha is combined with the CD137L, the activated NK cells can be further activated, so that the activity of the NK cells is higher, and the killing effect is stronger.

The invention provides an anti-leukemia pharmaceutical composition based on DNA damage activated NKT cells and application of the anti-leukemia pharmaceutical composition. A mouse leukemia model is adopted as a research object, and experimental results show that in a C1498 homotransplantation tumor C57BL / 6 immune sound mouse leukemia model, the tumor inhibition rate of a daunorubicin and alpha-galactosylceramide combined treatment group reaches 67.4%, the survival time is remarkably prolonged, and obvious toxicity is not caused; in a C57 mouse leukemia model constructed by caudal vein injection of C1498, daunorubicin and alpha-galactosylceramide are combined to treat and reverse leukemia-related hepatosplenomegaly (the weight of liver and spleen is equivalent to that of a normal group), leukocyte proliferation is inhibited, and the survival state of mice is improved. The invention provides a new direction for treatment of leukemia.