Advertisement

Synthesis and Vaccine Evaluation of the Tumor Associated Carbohydrate Antigen RM2 from Prostate Cancer

  • Hong-Yang Chuang
Book

Part of the Springer Theses book series (Springer Theses)

About this book

Introduction

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 α-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 dibranched galactoside unit is very challenging and the β-selective and efficient glycosylation of the galactosamine moiety at the 4-position of dibranched galactose is also problematic.

Keywords

Cancer-associated antigen Carbohydrate-based vaccine Disialogangliosides Glycolipid adjuvant Immunological adjuvants Monoclonal antibody RM2 Multivalent carbohydrate-protein interaction Prostate cancer Synthesis of glycoconjugates

Authors and affiliations

  • Hong-Yang Chuang
    • 1
  1. 1.Department of ChemistryNational Taiwan UniversityTaipeiTaiwan

Bibliographic information

  • DOI https://doi.org/10.1007/978-3-662-46848-7
  • Copyright Information Springer-Verlag Berlin Heidelberg 2015
  • Publisher Name Springer, Berlin, Heidelberg
  • eBook Packages Chemistry and Materials Science
  • Print ISBN 978-3-662-46847-0
  • Online ISBN 978-3-662-46848-7
  • Series Print ISSN 2190-5053
  • Series Online ISSN 2190-5061
  • Buy this book on publisher's site