Carbohydrate-monophosphoryl lipid a conjugates are fully synthetic self-adjuvanting cancer vaccines eliciting robust immune responses in the mouse.
Tumor-associated carbohydrate antigens (TACAs) are useful targets in the development of therapeutic cancer vaccines. However, a serious problem with them is the poor immunogenicity. To overcome the problem, a monophosphorylated derivative of Neisseria meningitidis lipid A was explored as a potential carrier molecule and built-in adjuvant for the construction of structurally defined fully synthetic glycoconjugate vaccines. Some paradigm-shifting discoveries about the monophosphoryl lipid A (MPLA)-TACA conjugates were that they elicited robust IgG antibody responses, indicating T cell-mediated immunity, without an external adjuvant and that an external adjuvant, e.g., Titermax Gold, actually reduced rather than promoted the immunological activity of the conjugates. The induced antibodies were proved to bind selectively to target tumor cells. MPLA was therefore demonstrated to be a powerful built-in immunostimulant and adjuvant for an all new design of fully synthetic glycoconjugate cancer vaccines.
Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States.
Qianli
Q
Wang
Zhifang
Z
Zhou
Shouchu
S
Tang
Zhongwu
Z
Guo
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D005679:G(M3) Ganglioside / Q000737:chemistry / Q000276:immunology*; D006001:Glycoconjugates / Q000008:administration & dosage / Q000138:chemical synthesis; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis; D008050:Lipid A / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009345:Neisseria meningitidis / Q000737:chemistry; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000737:chemistry
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D005679:G(M3) Ganglioside; D006001:Glycoconjugates; D007074:Immunoglobulin G; D008050:Lipid A; D014614:Vaccines, Synthetic; C048436:monophosphoryl lipid A