Sialyl-Tn Polysaccharide A1 as an Entirely Carbohydrate Immunogen: Synthesis and Immunological Evaluation

J Am Chem Soc. 2016 Nov 2;138(43):14264-14272. doi: 10.1021/jacs.6b05675. Epub 2016 Oct 21.

Abstract

Sialyl Thomsen-nouveau (STn) is a tumor-associated carbohydrate antigen (TACA) that is overexpressed in a variety of carcinomas such as breast, ovarian, and colon cancer. In normal tissue, STn is not detectable, which is critical for opportunities in developing cancer immunotherapies. A novel, entirely carbohydrate, semisynthetic STn-polysaccharide (PS) A1 conjugate was prepared and evaluated in C57BL/6 mice. STn-PS A1 was combined with commercially available monophosphoryl lipid A-based adjuvant, and after immunization, ELISA indicated a strong immune response for inducing anti-STn IgM/IgG antibodies. The specificity of these antibodies was concomitantly investigated using FACS analysis, and the results indicated excellent cell surface binding events to STn-expressing cancer cell lines MCF-7 and OVCAR-5. An INF-γ ELISpot assay was conducted to further confirm a robust cellular immunity invoked by STn-PS A1. Most importantly, the raised antibodies conferred complement-dependent cellular cytotoxicity against MCF-7 and OVCAR-5 cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Tumor-Associated, Carbohydrate / chemistry*
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Chemistry Techniques, Synthetic
  • Humans
  • MCF-7 Cells
  • Mice
  • Oximes / chemistry
  • Polysaccharides / chemistry*

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Oximes
  • Polysaccharides
  • sialosyl-Tn antigen