title: Boosting immunity to small tumor-associated carbohydrates with bacteriophage qβ capsids.
abstract: The development of an effective immunotherapy is an attractive strategy toward cancer treatment. Tumor associated carbohydrate antigens (TACAs) are overexpressed on a variety of cancer cell surfaces, which present tempting targets for anticancer vaccine development. However, such carbohydrates are often poorly immunogenic. To overcome this challenge, we show here that the display of a very weak TACA, the monomeric Tn antigen, on bacteriophage Qβ virus-like particles elicits powerful humoral responses to the carbohydrate. The effects of adjuvants, antigen display pattern, and vaccine dose on the strength and subclasses of antibody responses were established. The local density of antigen rather than the total amount of antigen administered was found to be crucial for induction of high Tn-specific IgG titers. The ability to display antigens in an organized and high density manner is a key advantage of virus-like particles such as Qβ as vaccine carriers. Glycan microarray analysis showed that the antibodies generated were highly selective toward Tn antigens. Furthermore, Qβ elicited much higher levels of IgG antibodies than other types of virus-like particles, and the IgG antibodies produced reacted strongly with the native Tn antigens on human leukemia cells. Thus, Qβ presents a highly attractive platform for the development of carbohydrate-based anticancer vaccines.
authors.affiliation: Department of Chemistry, Chemistry Building, Room 426, 578 South Shaw Lane, Michigan State University , East Lansing, Michigan 48824, United States.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Yin
authors.forename: Marta
authors.initials: M
authors.lastname: Comellas-Aragones
authors.forename: Sudipa
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Philip
authors.initials: P
authors.lastname: Bentley
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kaczanowska
authors.forename: Lbachir
authors.initials: L
authors.lastname: Benmohamed
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Gildersleeve
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
authors.forename: Xuefei
authors.initials: X
authors.lastname: Huang
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000008:administration & dosage / Q000276:immunology*; D001435:Bacteriophages / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D005260:Female; D006801:Humans; D007109:Immunity; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control
chemical_list: D000276:Adjuvants, Immunologic; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D007074:Immunoglobulin G; C040286:Tn antigen