Immunogenicity study of Globo H analogues with modification at the reducing or nonreducing end of the tumor antigen.
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.
Genomics Research Center, Academia Sinica , 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan.
Hsin-Yu
HY
Lee
Chien-Yu
CY
Chen
Tsung-I
TI
Tsai
Shiou-Ting
ST
Li
Kun-Hsien
KH
Lin
Yang-Yu
YY
Cheng
Chien-Tai
CT
Ren
Ting-Jen R
TJ
Cheng
Chung-Yi
CY
Wu
Chi-Huey
CH
Wong
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D002236:Carbohydrate Conformation; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; C472765:Globo-H