SialylTn-mAb17-1A carbohydrate-protein conjugate vaccine: effect of coupling density and presentation of SialylTn.
Carbohydrate antigens resulting from aberrant glycosylation of tumor cells, such as SialylTn, represent attractive targets for cancer vaccination. However, T-cell-independent carbohydrate antigens are poorly immunogenic and fail to induce memory and IgG class switch. Clustered expression patterns of some carbohydrates on the cell surface add further complexity to the design of carbohydrate-based vaccines. We describe here a vaccine consisting of SialylTn carbohydrate epitopes coupled to a highly immunogenic carrier molecule, mAb17-1A, adsorbed on alhydrogel and coformulated with a strong adjuvant, QS-21. The SialylTn-mAb17-1A conjugate vaccine was administered in Rhesus monkeys, and the immune responses against mAb17-1A, SialylTn, ovine submaxillary mucin, and tumor cells were analyzed. The data demonstrate that the density of carbohydrate epitopes on the carrier is an essential parameter for induction of anti-carbohydrate specific memory IgG immune responses. Furthermore, the influence of different types of presentation of SialylTn (monomeric vs trimers vs clustered via a branched polyethylenimine linker) on antibody titers and specificity was studied. High-density coupling of SialylTn epitopes to mAb17-1A induced the strongest immune response against synthetic SialylTn and showed also the highest reactivity against natural targets, such as OSM and tumor cells.
Kircheis
Ralf
R
igeneon AG, Immunotherapy of Cancer, Vienna, Austria. ralf.kircheis@igeneon.com
Vondru
Petra
P
Nechansky
Andreas
A
Ohler
Renate
R
Loibner
Hans
H
Himmler
Gottfried
G
Mudde
Geert C
GC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000918:Antibody Specificity; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000008:administration & dosage / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D000939:Epitopes; D018796:Immunoconjugates / Q000008:administration & dosage*; D007074:Immunoglobulin G; D007156:Immunologic Memory; D008253:Macaca mulatta; D018074:Vaccines, Conjugate / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D000939:Epitopes; D018796:Immunoconjugates; D007074:Immunoglobulin G; D018074:Vaccines, Conjugate; C055491:sialosyl-Tn antigen