Synthesis and Vaccine Evaluation of the Tumor Associated Carbohydrate Antigen RM2 from Prostate Cancer
Date Issued
2013
Date
2013
Author(s)
Chuang, Hong-Yang
Abstract
Prostate cancer is the most commonly diagnosed cancer among men and the RM2 antigen has been discovered as a member of an antigenic carbohydrates family that is highly expressed on prostate cancer cells. The novel antigen RM2 belongs to ‘‘ganglio-series’’and the ‘‘disialyl lacto-series type chain’’ groups. And the RM2 antigen was not been synthesized by chemical method before.
In this thesis, we have successfully developed a [1+2+3] one-pot strategy to synthesize the RM2 antigen hexasaccharide that was proposed to be a prostate tumor antigen. The structure of the synthetic product was verified by NMR analysis and antibody binding assay using a glycan microarray. In addition, the synthetic antigen was conjugated to a mutated diphtheria toxin (DT, CRM197) with different copy numbers and adjuvant combination to form the vaccine candidates. After vaccination in mice, we used glycan microarrays to monitor their immune response, and the results indicated that when one molecule of DT was incorporated with 4.7 molecules of RM2 in average (DT-RM4.7) and adjuvanted with the glycolipid C34 exhibited the strongest anti-RM2 IgG titer. Moreover, the induced mouse antibodies mediated effective complement-dependent cytotoxicity (CDC) against the prostate cancer cell line LNCap.
Subjects
攝護腺癌
疫苗
全合成
SDGs
Type
thesis
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