A fully synthetic therapeutic vaccine candidate targeting carcinoma-associated Tn carbohydrate antigen induces tumor-specific antibodies in nonhuman primates.
We recently developed an efficient strategy based on a fully synthetic dendrimeric carbohydrate display (multiple antigenic glycopeptide; MAG) to induce anticarbohydrate antibody responses for therapeutic vaccination against cancer. Here, we show the superior efficacy of the MAG strategy over the traditional keyhole limpet hemocyanin glycoconjugate to elicit an anticarbohydrate IgG response against the tumor-associated Tn antigen. We highlight the influence of the aglyconic carrier elements of such a tumor antigen for their recognition by the immune system. Finally, we additionally developed the MAG system by introducing promiscuous HLA-restricted T-helper epitopes and performed its immunological evaluation in nonhuman primates. MAG:Tn vaccines induced in all of the animals strong tumor-specific anti-Tn antibodies that can mediate antibody-dependent cell cytotoxicity against human tumor. Therefore, the preclinical evaluation of the MAG:Tn vaccine demonstrates that it represents a safe and highly promising immunotherapeutic molecularly defined tool for targeting breast, colon, and prostate cancers that express the carbohydrate Tn antigen.
Lo-Man
Richard
R
Unité de Biologie des Régulations Immunitaires (Institut National de la Santé et de la Recherche Médicale E352) Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris, France. rloman@pasteur.fr
Vichier-Guerre
Sophie
S
Perraut
Ronald
R
Dériaud
Edith
E
Huteau
Valérie
V
BenMohamed
Lbachir
L
Diop
Ousmane M
OM
Livingston
Philip O
PO
Bay
Sylvie
S
Leclerc
Claude
C
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002522:Chlorocebus aethiops; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006020:Glycopeptides / Q000737:chemistry / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology*; D016233:Immunotherapy, Active / Q000379:methods*; D008251:Macaca; D051379:Mice; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006020:Glycopeptides; D018796:Immunoconjugates; C040286:Tn antigen; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin