Immunization of Rhesus monkeys with a SialylTn-mAb17-1A conjugate vaccine co-formulated with QS-21 induces a temporary systemic cytokine release and NK cytotoxicity against tumor cells.
Tumor-associated antigens resulting from aberrant glycosylation, such as the SialylTn carbohydrate antigen, are frequently over-expressed on cancer cells and provide potential targets for cancer vaccination. Immunization of Rhesus monkeys with SialylTn coupled to a highly immunogenic carrier molecule and formulated on aluminum hydroxide induced a strong immune response against the carrier protein but only a moderate IgM immune response against the SialylTn carbohydrate antigen. Co-formulation with QS-21 adjuvant dramatically enhanced the anti-SialylTn immune response and resulted in a SialylTn-specific IgG switch. The kinetics of the carbohydrate-specific IgG response correlated with a temporary release of cytokines such as IFNgamma, IL-2, IL-1beta, TNFalpha and GM-CSF which was measurable in the immune serum by xMAP Multiplex technology. Furthermore, tumor cell killing by activated natural killer cells was induced. These data demonstrate that immunization with a tumor-associated carbohydrate antigen in a highly immunogenic formulation results in a temporary release of type 1 cytokines which may be required for the induction of a specific IgG immune response against the carbohydrate antigen as well as for activation of effector cells against tumor cells.
Kircheis
Ralf
R
Igeneon GmbH, Immunotherapy of Cancer, Brunnerstrasse 69/3, 1230 Vienna, Austria. ralf.kircheis@yahoo.com
Siegl
Petra
P
Grunt
Susanne
S
Halanek
Nicole
N
Loibner
Hans
H
Mudde
Geert C
GC
Nechansky
Andreas
A
D000276:Adjuvants, Immunologic; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D012503:Saponins / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D016207:Cytokines; D007074:Immunoglobulin G; D012503:Saponins; D018074:Vaccines, Conjugate; C078785:saponin QA-21V1