Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer.
Globo H (GH) is a hexasaccharide specifically overexpressed on a variety of cancer cells and therefore, a good candidate for cancer vaccine development. To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked GH to a carrier protein, including keyhole limpet hemocyanion, diphtheria toxoid cross-reactive material (CRM) 197 (DT), tetanus toxoid, and BSA, and combined with an adjuvant, and it was administered to mice for the study of immune response. Glycan microarray analysis of the antiserum obtained indicated that the combination of GH-DT adjuvanted with the α-galactosylceramide C34 has the highest enhancement of anti-GH IgG. Compared with the phase III clinical trial vaccine, GH-keyhole limpet hemocyanion/QS21, the GH-DT/C34 vaccine elicited more IgG antibodies, which are more selective for GH and the GH-related epitopes, stage-specific embryonic antigen 3 (SSEA3) and SSEA4, all of which were specifically overexpressed on breast cancer cells and breast cancer stem cells with SSEA4 at the highest level (>90%). We, therefore, further developed SSEA4-DT/C34 as a vaccine candidate, and after immunization, it was found that the elicited antibodies are also IgG-dominant and very specific for SSEA4.
Genomics Research Center and Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program,  Academia Sinica, Taipei 115,  Taiwan.
Yen-Lin
YL
Huang
Jung-Tung
JT
Hung
Sarah K C
SK
Cheung
Hsin-Yu
HY
Lee
Kuo-Ching
KC
Chu
Shiou-Ting
ST
Li
Yu-Chen
YC
Lin
Chien-Tai
CT
Ren
Ting-Jen R
TJ
Cheng
Tsui-Ling
TL
Hsu
Alice L
AL
Yu
Chung-Yi
CY
Wu
Chi-Huey
CH
Wong
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000737:chemistry*; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins; D007106:Immune Sera / Q000032:analysis; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D046228:Microarray Analysis; D015394:Molecular Structure; D014411:Neoplastic Stem Cells / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055746:Stage-Specific Embryonic Antigens / Q000276:immunology*; D013745:Tetanus Toxoid
D015295:Antigens, Tumor-Associated, Carbohydrate; D001426:Bacterial Proteins; D019496:Cancer Vaccines; C472765:Globo-H; D007106:Immune Sera; D007074:Immunoglobulin G; D055746:Stage-Specific Embryonic Antigens; D013745:Tetanus Toxoid; C052924:stage-specific embryonic antigen-3; C066584:stage-specific embryonic antigen-4; C028581:CRM197 (non-toxic variant of diphtheria toxin); D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin