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    • 1. 发明申请
    • GLOBO H AND RELATED ANTI-CANCER VACCINES WITH NOVEL GLYCOLIPID ADJUVANTS
    • GLOBO H和相关的抗癌药物与新型甘露醇辅剂
    • US20100136042A1
    • 2010-06-03
    • US12537129
    • 2009-08-06
    • Chi-Huey WongChung-Yi WuAlice YuJohn Yu
    • Chi-Huey WongChung-Yi WuAlice YuJohn Yu
    • A61K39/385A61P35/04
    • A61K39/0011A61K2039/55511A61K2039/6037A61K2039/6081A61K2039/627C12N15/1137C12N2310/14
    • 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 CD1d on a dendritic cell, such as an α-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-CRM197) 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-CRM197.
    • 提供免疫原性组合物,癌症疫苗和治疗癌症的方法。 组合物,其包含:(a)聚糖如Globo H或其免疫原性片段,其中所述聚糖通过诸如对硝基苯基之类的接头与载体蛋白缀合; 和(b)包含能够结合树突状细胞上的CD1d的糖脂如α-半乳糖基 - 神经酰胺衍生物的佐剂,其中所述免疫原性组合物诱导与IgM同种型相比诱导更高相对水平的IgG同种型抗体的免疫应答 抗体。 提供了包含载体蛋白质白喉毒素交叉反应材料197(DT-CRM197)和佐剂C34的免疫原性组合物。 由本文公开的免疫原性组合物产生的抗体进一步中和至少一种抗原Globo H,阶段特异性胚胎抗原-3(SSEA-3)和阶段特异性胚胎抗原-4(SSEA-4)。 包括含有与DT-CRM197缀合的Globo H,SSEA-3或SSEA-4的免疫原性组合物的乳腺癌干细胞的治疗剂。
    • 5. 发明申请
    • Alpha-galactosyl ceramide analogs and their use as immunotherapies
    • α-半乳糖基神经酰胺类似物及其作为免疫治疗的用途
    • US20080260774A1
    • 2008-10-23
    • US12082751
    • 2008-04-14
    • Chi-Huey WongAlice YuYa-Jen Chang
    • Chi-Huey WongAlice YuYa-Jen Chang
    • A61K39/00A61K31/35C07D315/00A61P37/00
    • C07H15/26A61K8/68A61K2800/91A61Q17/005C07H15/06C07H15/18
    • 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: wherein, n is 0 to 25; X is selected from O and S; R1 is selected from H, CH3, and phenyl, where phenyl is optionally substituted with H, OH, OCH3, F, CF3, phenyl, phenyl-F, C1-C6 alkyl, or C2-C6 branched alkyl; R2 is selected from OH and H; R3 is selected from C1-C15 alkyl, and phenyl, where phenyl is optionally substituted with H, OH, OCH3, F, CF3, phenyl, C1-C6 alkyl, or C2-C6 branched alkyl; R4 is selected from OH, OSO3H, OSO3Na, and OSO3K; and R5 is selected from CH2OH and CO2H; 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.
    • 本公开涉及合成的α-半乳糖神经酰胺(α-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,并且在 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: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。