Development of Globo H anti-breast cancer vaccines with novel glycolipid adjuvants
Date Issued
2008
Date
2008
Author(s)
Huang, Yen-Lin
Abstract
Aberrant glycosylation is often a hallmark during tumor progression and correlates with poor prognosis. Diverse tumor associated antigens existed in the form of glycolipids or glycoproteins have been characterized. Globo H (Fucα1→2Galβ1→3 GalNAcβ1→3Galα1→4Galβ1→4Glu) hexasaccharide was first isolated from metastatic breast cancer cells by Hakomori in 1984 and initially synthesized by Danishefsky using glycal assembly strategy in 1995. Globo H was present on most cancers of epithelial origin, but only minimal expression on normal secretory tissue which is not readily accessible to immune system. Taking advantage of the exclusive expression signature, Globo H has been an attractive target for immunotherapy against prostate, breast, colon and ovarian cancers. Although, numerous vaccines are undergoing clinical evaluation and some shows improved survival rate in patients, the ultimate goal is to prevent the tumor recurrence. Therefore, we aim to develop a more effective vaccine and adjuvant against a variety of cancers.ere we reported the promising carbohydrate based vaccine containing Globo H (B cell epitope) chemically conjugated to the immunogenic carrier DT CRM197 (Th epitope) via a p-nitrophenyl linker and can be subsequently characterized by MALDI-TOF analysis. The synthetic vaccines collaborated with novel glycolipid derivatives functioned as immunological adjuvants provided the exceptional immunogenicity in both BALB/c and C57BL/6 models. Additionally, vaccination with glycolipids showed enhanced IgG, IgG1 and IgM production and delayed tumorigenesis in xenograft studies. Overall, systematic optimization with respect to formulation, adjuvant, dosage, glycan/protein ratio and timing of immunization regimen may further improve the protection against tumors. Finally, conjugation of diverse carbohydrate antigens to various carriers or dendrimer will be planned in the near further.
Subjects
breast cancer
vaccine
glycolipid
adjuvants
SDGs
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