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Synthesis and Vaccine Evaluation of the Tumor Associated Carbohydrate Antigen RM2 from Prostate Cancer (Hardcover, 2015 ed.)
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Synthesis and Vaccine Evaluation of the Tumor Associated Carbohydrate Antigen RM2 from Prostate Cancer (Hardcover, 2015 ed.)
Series: Springer Theses
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This thesis focuses on the synthesis and vaccine evaluation of the
prostate tumor- associated carbohydrate antigen RM2. The author
first presents the use of the [1+2+3] one-pot sequential strategy
to successfully synthesise the RM2 antigen and its analogues as
single stereoisomers in every glycosylation step, producing good
yields and stereoselectivity. He then introduces the conjugation of
the synthetic RM2 antigen to the carrier protein CRM197 in an
average number of 1-10 to create the prostate cancer vaccine
candidate, which is combined with -galactosylceramide C1, its
analogue C34, or Alu. The results of the vaccination studies in
mice are also described and indicate that the strongest anti-RM2
antigen titer is exhibited when one molecule of diphtheria toxin
(DT) is conjugated with an average of 4.7 molecules of RM2 antigen
(DT-RM4.7) and adjuvanted with the glycolipid C34. More
importantly, the induced mouse antibodies mediate the effective
complement-dependent cytotoxicity (CDC) against the prostate cancer
cell line LNCap. The study presented in this thesis is the first
ever to successfully synthesize this complex glycan molecule. Owing
to the steric hindrance of the adjacent sialyl moiety, the
introduction of two sialic acid units to the compact and rigid 3,4
di branched galactoside unit is very challenging and the -selective
and efficient glycosylation of the galactosamine moiety at the
4-position of di branched galactose is also problematic.
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