WONG, CHI HUEY,翁启惠,翁啟惠,WU, CHUNG YI,吴宗益,吳宗益,CHEN, ALICE,陈铃津,陳鈴津,YU, JOHN,游正博,游正博
申请号:
TW098127948
公开号:
TWI392502B
申请日:
2009.08.19
申请国别(地区):
TW
年份:
2013
代理人:
摘要:
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.本發明提供免疫原性組合物、癌症疫苗、以及用以治療癌症之方法。本發明提供組合物,其包含:(a)聚醣,諸如,Globo H,或其免疫原性片段,其中該聚醣係經由連接子(諸如,對-硝基苯基)而與載體蛋白共軛連結;及(b)佐劑,其包含可結合樹狀細胞上之CD1d的醣脂質,諸如,α-半乳糖苷基-神經醯胺衍生物,其中該免疫原性組合物可誘發免疫反應,該免疫反應可誘發相較於IgM同種型抗體之較高相對含量的IgG同種型抗體。本發明提供免疫原性組合物,其包含載體蛋白白喉毒素交叉反應性材料197(DT-CRM197)以及佐劑C34。本文所揭示之免疫原性組合物所產生之抗體可進一步中和抗原Globo H、階段特異性胚胎抗原-3(SSEA-3)、階段特異性胚胎抗原-4(SSEA-4)中之至少一種。本發明亦提供對抗乳癌幹細胞之治療劑,其包含免疫原性組合物,該等組合物包含與DT-CRM197共軛連結之Globo H、SSEA-3、或SSEA-4。