title: Chemical Synthesis of GM2 Glycans, Bioconjugation with Bacteriophage Qβ, and the Induction of Anticancer Antibodies.
abstract: The development of carbohydrate-based antitumor vaccines is an attractive approach towards tumor prevention and treatment. Herein, we focused on the ganglioside GM2 tumor-associated carbohydrate antigen (TACA), which is overexpressed in a wide range of tumor cells. GM2 was synthesized chemically and conjugated with a virus-like particle derived from bacteriophage Qβ. Although the copper-catalyzed azide-alkyne cycloaddition reaction efficiently introduced 237 copies of GM2 per Qβ, this construct failed to induce significant amounts of anti-GM2 antibodies compared to the Qβ control. In contrast, GM2 immobilized on Qβ through a thiourea linker elicited high titers of IgG antibodies that recognized GM2-positive tumor cells and effectively induced cell lysis through complement-mediated cytotoxicity. Thus, bacteriophage Qβ is a suitable platform to boost antibody responses towards GM2, a representative member of an important class of TACA: the ganglioside.
authors.affiliation: Department of Chemistry, Michigan State University, 578 S. Shaw Lane, Room 426, East Lansing, MI, 48824-1322, USA.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Chemistry, Michigan State University, 578 S. Shaw Lane, Room 426, East Lansing, MI, 48824-1322, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Dulaney
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332-0400, USA.
authors.forename: Craig S
authors.initials: CS
authors.lastname: McKay
authors.affiliation: Department of Chemistry, Michigan State University, 578 S. Shaw Lane, Room 426, East Lansing, MI, 48824-1322, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Baniel
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332-0400, USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kaczanowska
authors.affiliation: Department of Chemistry, Michigan State University, 578 S. Shaw Lane, Room 426, East Lansing, MI, 48824-1322, USA.|Chemistry Department, Faculty of Science, Benha University, Benha, Qaliobiya, Egypt.
authors.forename: Sherif
authors.initials: S
authors.lastname: Ramadan
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332-0400, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
authors.affiliation: Department of Chemistry, Michigan State University, 578 S. Shaw Lane, Room 426, East Lansing, MI, 48824-1322, USA. xuefei@chemistry.msu.edu.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Huang
mesh_terms: D017908:Allolevivirus / Q000737:chemistry*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000737:chemistry; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005678:G(M2) Ganglioside / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D005678:G(M2) Ganglioside
keywords: antibodies; carbohydrates; immunology; synthesis; vaccines