title: Sialyl-Tn Polysaccharide A1 as an Entirely Carbohydrate Immunogen: Synthesis and Immunological Evaluation.
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.
authors.affiliation: Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo , 2801 West Bancroft Street, Toledo, Ohio 43606, United States.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo , 2801 West Bancroft Street, Toledo, Ohio 43606, United States.
authors.forename: Kristopher A
authors.initials: KA
authors.lastname: Kleski
authors.affiliation: Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo , 2801 West Bancroft Street, Toledo, Ohio 43606, United States.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Trabbic
authors.affiliation: Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo , 2801 West Bancroft Street, Toledo, Ohio 43606, United States.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bourgault
authors.affiliation: Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo , 2801 West Bancroft Street, Toledo, Ohio 43606, United States.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Andreana
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology*; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D010091:Oximes / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D010091:Oximes; D011134:Polysaccharides; C055491:sialosyl-Tn antigen