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.
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| Abstract |
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.
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| Authors | Ralf Kircheis, Petra Siegl, Susanne Grunt, Nicole Halanek, Hans Loibner, Geert C Mudde, Andreas Nechansky |
| Journal | Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 56 Issue 6 Pg. 863-73 (Jun 2007) ISSN: 0340-7004 [Print] Germany |
| PMID | 17009044 (Publication Type: Journal Article) |
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