Immunogenicity Study of Globo H Analogues with Modification at the Reducing or Nonreducing End of the Tumor Antigen

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• 作者：Hsin-Yu Lee ; Chien-Yu Chen ; Tsung-I Tsai ; Shiou-Ting Li ; Kun-Hsien Lin ; Yang-Yu Cheng ; Chien-Tai Ren ; Ting-Jen R. Cheng ; Chung-Yi Wu ; Chi-Huey Wong
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：December 3, 2014
• 年：2014
• 卷：136
• 期：48
• 页码：16844-16853
• 全文大小：655K
• ISSN：1520-5126

文摘

Globo H-based therapeutic cancer vaccines have been tested in clinical trials for the treatment of late stage breast, ovarian, and prostate cancers. In this study, we explored Globo H analogue antigens with an attempt to enhance the antigenic properties in vaccine design. The Globo H analogues with modification at the reducing or nonreducing end were synthesized using chemoenzymatic methods, and these modified Globo H antigens were then conjugated with the carrier protein diphtheria toxoid cross-reactive material (CRM) 197 (DT), and combined with a glycolipid C34 as an adjuvant designed to induce a class switch to form the vaccine candidates. After Balb/c mice injection, the immune response was studied by a glycan array and the results showed that modification at the C-6 position of reducing end glucose of Globo H with the fluoro, azido, or phenyl group elicited IgG antibody response to specifically recognize Globo H (GH) and the GH-related epitopes, stage-specific embryonic antigen 3 (SSEA3) (also called Gb5) and stage-specific embryonic antigen 4 (SSEA4). However, only the modification of Globo H with the azido group at the C-6 position of the nonreducing end fucose could elicit a strong IgG immune response. Moreover, the antibodies induced by these vaccines were shown to recognize GH expressing tumor cells (MCF-7) and mediate the complement-dependent cell cytotoxicity against tumor cells. Our data suggest a new potential approach to cancer vaccine development.