公开(公告)号：JP2014144958A

公开(公告)日：2014-08-14

申请号：JP2014035431

申请日：2014-02-26

Applicant: Academia Sinica ,  アカデミア シニカAcademia Sinica

Inventor： WONG CHI-HUEY ,  WU CHUNG-YI ,  YU ALICE ,  YU JOHN

IPC: A61K39/00 ,  A61K39/385 ,  A61K39/39 ,  A61P35/00

CPC classification number: A61K39/0011 ,  A61K2039/55511 ,  A61K2039/6037 ,  A61K2039/6081 ,  A61K2039/627 ,  C12N15/1137 ,  C12N2310/14

Abstract: PROBLEM TO BE SOLVED: To provide: an immunogenic composition capable of high levels of immune responses immune-targeting glycolipid antigen Globo H, which is a tumor associated sugar chain; a cancer vaccine; and a method of treating cancer.SOLUTION: The invention relates to an immunogenic composition comprising: (a) a sugar chain such as Globo H or an immunogenic fragment thereof conjugated with a carrier protein comprising diphtheria toxin cross-reacting material 197 (DT-CRM 197) through a linker such as p-nitrophenol; and (b) an adjuvant with the following structure comprising a glycolipid capable of binding CD1d on a dendritic cell such as an α-galactosyl ceramide derivative.

Abstract translation: 要解决的问题：提供：能够高水平免疫应答的免疫原性组合物免疫靶向糖脂抗原Globo H，其是肿瘤相关糖链; 癌症疫苗; 和一种治疗癌症的方法。解决方案：本发明涉及免疫原性组合物，其包含：（a）糖链，例如Globo H或其与包含白喉毒素交叉反应材料197（DT-CRM）的载体蛋白缀合的免疫原性片段 197）通过接头如对硝基苯酚; 和（b）具有以下结构的佐剂，其包含能够结合树突状细胞如α-半乳糖基神经酰胺衍生物上的CD1d的糖脂。

公开(公告)号：ES2545969T3

公开(公告)日：2015-09-17

申请号：ES09795269

申请日：2009-07-10

Applicant: ACADEMIA SINICA

Inventor： WONG CHI-HUEY ,  YU ALICE ,  CHANG YA-JEN ,  LIN KUN-HSIEN ,  CHENG EDMOND Y S ,  JAN JIA-TSRONG ,  LIN YI-LING ,  HUNG JUNG-TUNG

IPC: C07H15/18 ,  A61K31/70 ,  A61K31/7034 ,  A61K39/00 ,  A61K39/39 ,  A61P31/04 ,  A61P31/16 ,  A61P35/00

Abstract: Un compuesto representado por la estructura de fórmula 1:**Fórmula** o una sal farmacéuticamente aceptable del mismo; para su uso en medicina.

公开(公告)号：ZA201101128B

公开(公告)日：2013-11-27

申请号：ZA201101128

申请日：2011-02-11

Applicant: ACADEMIA SINICA

Inventor： WONG CHI-HUEY ,  YU ALICE ,  CHANG YA-JEN ,  LIN KUN-HSIEN ,  HUNG JUNG-TUNG

IPC: A61K20060101 ,  A61P20060101

Abstract: The present disclosure relates to synthetic alpha-galactosyl ceramide (α-GalCer) analogs, and their use as immunotherapies. In one aspect. a method of activating a cytokine response in a subject includes administering an effective amount of a compound to a subject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula 1: or a pharmaceutically acceptable salt thereof; forming a complex between the compound and the antigen-presenting cell, wherein the formation of the complex results in the activation of a receptor on the lymphocyte; and activating the lymphocyte to produce the cytokine response.

公开(公告)号：AU2014201215B2

公开(公告)日：2016-05-05

申请号：AU2014201215

申请日：2014-03-05

Applicant: ACADEMIA SINICA

Inventor： WONG CHI-HUEY ,  WU CHUNG-YI ,  YU ALICE ,  YU JOHN

IPC: A61K39/00 ,  A61K39/385

Abstract: The present invention provides for an immunogenic composition comprising (a) a glycan, such as Globo H, stage-specific embryonic antigen-3 (SSEA-3) or SSEA-4, conjugated to a carrier protein through a linker; (b) an adjuvant comprising a glycolipid, such as a-galactosyl-ceramide adjuvant, wherein the composition induces an immune response, such as a higher relative level of IgG isotype antibodies compared to IgM isotype antibodies, or neutralising antibodies against at least one antigen selected from the group consisting of Globo H, Gb4, SSEA-3, and SSEA-4. Uses of the immunogenic composition for treating or inhibiting tumour growth are also provided.

公开(公告)号：DK2320947T3

公开(公告)日：2015-09-07

申请号：DK09795269

申请日：2009-07-10

Applicant: ACADEMIA SINICA

Inventor： WONG CHI-HUEY ,  YU ALICE ,  LIN KUN-HSIEN ,  CHENG EDMOND Y S ,  JAN JIA-TSRONG ,  LIN YI-LING ,  HUNG JUNG-TUNG ,  CHANG YA-JEN

IPC: A61K31/70 ,  C07H15/18 ,  A61K31/7034 ,  A61K39/00 ,  A61K39/39 ,  A61P31/04 ,  A61P31/16 ,  A61P35/00

公开(公告)号：WO2010006315A3

公开(公告)日：2010-03-25

申请号：PCT/US2009050328

申请日：2009-07-10

Applicant: ACADEMIA SINICA ,  WONG CHI-HUEY ,  YU ALICE ,  CHANG YA-JEN ,  LIN KUN-HSIEN ,  CHENG Y S EDMOND ,  JAN JIA-TSRONG ,  LIN YI-LING ,  HUNG JUNG-TUNG

Inventor： WONG CHI-HUEY ,  YU ALICE ,  CHANG YA-JEN ,  LIN KUN-HSIEN ,  CHENG Y S EDMOND ,  JAN JIA-TSRONG ,  LIN YI-LING ,  HUNG JUNG-TUNG

IPC: A61K39/39 ,  A61K31/70 ,  A61P31/04 ,  A61P31/16 ,  A61P35/00

CPC classification number: C07H15/18 ,  A61K31/7034 ,  A61K39/0011 ,  A61K2039/57

Abstract: The present disclosure relates to synthetic alpha-galactosyl ceramide (a- GalCer) analogs, and their use as immunotherapies, adjuvants, and antiviral, antibacterial, and anticancer agents. In one aspect, a method of activating a cytokine response in a subject includes administering an effective amount of a compound to a subject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula 1 :; or a pharmaceutically acceptable salt thereof; forming a complex between the compound and the antigen-presenting cell, wherein the formation of the complex results in the activation of a receptor on the lymphocyte; and activating the lymphocyte to produce the cytokine response.

Abstract translation: 本公开内容涉及合成的α-半乳糖神经酰胺（a-GalCer）类似物，以及它们作为免疫疗法，佐剂和抗病毒，抗菌和抗癌剂的用途。 一方面，在受试者中激活细胞因子应答的方法包括向受试者施用有效量的化合物，其中所述受试者具有包括细胞群的适应性免疫系统，所述群体包括至少一种淋巴细胞和 至少一种抗原呈递细胞，并且其中所述化合物由式1的结构表示： 或其药学上可接受的盐; 在化合物和抗原呈递细胞之间形成复合物，其中复合物的形成导致淋巴细胞上受体的活化; 并激活淋巴细胞以产生细胞因子反应。

公开(公告)号：WO2008128207A1

公开(公告)日：2008-10-23

申请号：PCT/US2008060275

申请日：2008-04-14

Applicant: ACADEMIA SINICA ,  WONG CHI-HUEY ,  YU ALICE ,  CHANG YA-JEN

Inventor： WONG CHI-HUEY ,  YU ALICE ,  CHANG YA-JEN

IPC: A61K8/42 ,  A61K8/00 ,  C07C235/80 ,  C07C237/10

CPC classification number: C07H15/26 ,  A61K8/68 ,  A61K2800/91 ,  A61Q17/005 ,  C07H15/06 ,  C07H15/18

Abstract: The present disclosure relates to synthetic alpha-galactosyl ceramide (a-GalCer) analogs, and their use as immunotherapies. In one aspect, a method of activating a cytokine response in a subject includes administering an effective amount of a compound to a subject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula (1) wherein, n is 0 to 25; X is selected from O and S; R 1 is selected from H, CH 3 , and phenyl, where phenyl is optionally substituted with H, OH, OCH 3 , F, CF 3 , phenyl, phenyl-F, C 1 -C 6 alkyl, or C 2 -C 6 branched alkyl; R 2 is selected from OH and H; R 3 is selected from C 1 -C 15 alkyl, and phenyl, where phenyl is optionally substituted with H, OH, OCH 3 , F, CF 3 , phenyl, C 1 -C 6 alkyl, or C 2 -C 6 branched alkyl; R 4 is selected from OH, OSO 3 H, OSO 3 Na, and OSO 3 K; and R 5 is selected from CH 2 OH and CO 2 H; or a pharmaceutically acceptable salt thereof; forming a complex between the compound and the antigen-presenting cell, wherein the formation of the complex results in the activation of a receptor on the lymphocyte; and activating the lymphocyte to produce the cytokine response.

Abstract translation: 本公开内容涉及合成的α-半乳糖神经酰胺（a-GalCer）类似物，以及它们作为免疫治疗的用途。 一方面，在受试者中激活细胞因子应答的方法包括向受试者施用有效量的化合物，其中所述受试者具有包括细胞群的适应性免疫系统，所述群体包括至少一种淋巴细胞和 至少一个抗原呈递细胞，并且其中所述化合物由式（1）的结构表示，其中n为0至25; X选自O和S; R 1选自H，CH 3和苯基，其中苯基任选被H，OH，OCH 3，F，CF 苯基，苯基-F，C 1 -C 6烷基或C 2 -C 6亚烷基 >支链烷基; R 2选自OH和H; R 3选自C 1 -C 15烷基和苯基，其中苯基任选被H，OH，OCH 3取代， 3，F，CF 3，苯基，C 1 -C 6烷基或C 2 H 2 -C 6 -C 6支链烷基; R 4选自OH，OSO 3 H，OSO 3 Na和OSO 3 K; 和R 5选自CH 2 OH和CO 2 H; 或其药学上可接受的盐; 在化合物和抗原呈递细胞之间形成复合物，其中复合物的形成导致淋巴细胞上受体的活化; 并激活淋巴细胞以产生细胞因子反应。

公开(公告)号：WO2006044616A3

公开(公告)日：2006-08-24

申请号：PCT/US2005036961

申请日：2005-10-14

Applicant: ACADEMIA SINICA ,  WONG CHI-HUEY ,  HSU HSIEN-YEH ,  HUA KUO-FENG ,  LIN CHUN-HUNG ,  HSU JASON ,  CHEN SHUI-TEIN ,  LIN KUO-I ,  YANG WEN-BIN ,  YU JOHN ,  YU ALICE

Inventor： WONG CHI-HUEY ,  HSU HSIEN-YEH ,  HUA KUO-FENG ,  LIN CHUN-HUNG ,  HSU JASON ,  CHEN SHUI-TEIN ,  LIN KUO-I ,  YANG WEN-BIN ,  YU JOHN ,  YU ALICE

IPC: A01N65/00

CPC classification number: A61K36/074

Abstract: A fucose-containing glycoprotein fraction obtainable from an extract of Ganoderma Lucidum Reishi, compositions comprising the fuconse-containing glycoprotein fraction, a method to mediate immunomodulating events associated with IL-1 gene expression, a method to stimulate the expression of an inflammatory cytokine, a method to modulate protein kinase pathways associated with inflammatory cytokine Interleukin 1, a method to induce a TLR mediated event; a method to modulate differentiation of a mononuclear cell, a method to enhance cytotoxicity of an NK cell against an NK-sensitive tumor cell, a method to activate the expression of cytokines, a method to induce Blimp-1 expression in a mouse splenic B cell or human B cell, human mature splenocytes or dendritic cell, a method to inhibit LPS induced nitric oxide production in macrophages, a method to activate spleen cells proliferation, and a method to modify the proteome of a spleen cell.

Abstract translation: 从灵芝提取物获得的含岩藻糖的糖蛋白部分，包含含有蛋白质的糖蛋白部分的组合物，介导与IL-1基因表达相关的免疫调节事件的方法，刺激炎性细胞因子的表达的方法 调节与炎症细胞因子相关的蛋白激酶途径白细胞介素1的方法，诱导TLR介导的事件的方法; 调节单核细胞分化的方法，增强NK细胞对NK敏感性肿瘤细胞的细胞毒性的方法，激活细胞因子表达的方法，在小鼠脾B细胞中诱导Blimp-1表达的方法 或人B细胞，人成熟脾细胞或树突状细胞，抑制巨噬细胞中LPS诱导的一氧化氮产生的方法，活化脾细胞增殖的方法以及修饰脾细胞的蛋白质组的方法。

公开(公告)号：CA2728341C

公开(公告)日：2019-07-02

申请号：CA2728341

申请日：2009-08-06

Applicant: ACADEMIA SINICA

Inventor： WONG CHI-HUEY ,  WU CHUNG-YI ,  YU ALICE ,  YU JOHN

IPC: A61K39/00 ,  A61K39/385

Abstract: Immunogenic compositions, cancer vaccines and methods for treating cancer are provided. Compositions compris-ing: (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 compris-ing 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.

公开(公告)号：CA2756053A1

公开(公告)日：2010-01-14

申请号：CA2756053

申请日：2009-07-10

Applicant: ACADEMIA SINICA

Inventor： WONG CHI-HUEY ,  YU ALICE ,  CHANG YA-JEN ,  LIN KUN-HSIEN ,  CHENG Y S EDMOND ,  JAN JIA-TSRONG ,  LIN YI-LING ,  HUNG JUNG-TUNG

IPC: A61K39/39 ,  A61K31/70 ,  A61P31/04 ,  A61P31/16 ,  A61P35/00

Abstract: The present disclosure relates to synthetic alpha-galactosyl ceramide (.alpha.- GalCer) analogs, and their use as immunotherapies, adju-vants, and antiviral, antibacterial, and anticancer agents. In one aspect, a method of activating a cy-tokine response in a subject includes administer-ing an effective amount of a compound to a sub-ject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula 1 :; or a pharmaceutically acceptable salt thereof; forming a complex between the com-pound and the antigen-presenting cell, wherein the formation of the complex results in the activa-tion of a receptor on the lymphocyte; and activat-ing the lymphocyte to produce the cytokine re-sponse.