Synthetic multivalent glycopeptide-lipopeptide antitumor vaccines: impact of the cluster effect on the killing of tumor cells.
Multivalent synthetic vaccines were obtained by solid-phase synthesis of tumor-associated MUC1 glycopeptide antigens and their coupling to a Pam3 Cys lipopeptide through click reactions. These vaccines elicited immune responses in mice without the use of any external adjuvant. The vaccine containing four copies of a MUC1 sialyl-TN antigen showed a significant cluster effect. It induced in mice prevailing IgG2a antibodies, which bind to MCF-7 breast tumor cells and initiate the killing of these tumor cells by activation of the complement-dependent cytotoxicity complex.
Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (P.R. China).
Hui
H
Cai
Zhan-Yi
ZY
Sun
Mei-Sha
MS
Chen
Yu-Fen
YF
Zhao
Horst
H
Kunz
Yan-Mei
YM
Li
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D057930:Click Chemistry; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D008074:Lipoproteins / Q000138:chemical synthesis / Q000737:chemistry*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011817:Rabbits
D000906:Antibodies; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006020:Glycopeptides; D008074:Lipoproteins; D018396:Mucin-1; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine
antigens; antitumor agents; cytotoxicity; multivalent glycopeptides; vaccines