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    • 3. 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
    • WO2010005598A1
    • 2010-01-14
    • PCT/US2009/004519
    • 2009-08-06
    • ACADEMIA SINICAWONG, Chi-HueyWU, Chung-YiYU, AliceYU, John
    • WONG, Chi-HueyWU, Chung-YiYU, AliceYU, John
    • A61K39/00A61K39/385
    • 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 CDId 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-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.
    • 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)包含能够结合树突细胞上的CD1d的糖脂的佐剂,例如α-半乳糖基 - 神经酰胺衍生物,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-CRM 197)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-CRM 197结合的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。