Immunization of Rhesus monkeys with the conjugate vaccine IGN402 induces an IgG immune response against carbohydrate and protein antigens, and cancer cells

Tumor-associated antigens resulting from aberrant glycosylation, such as the SialylTn carbohydrate antigen, are over-expressed on cancer cells and provide potential targets for cancer vaccination. However, as T-cell-independent antigens carbohydrates are poorly immunogenic, and fail to induce memory. In order to increase the immunogenicity we have coupled the SialylTn carbohydrate antigen to a highly immunogenic carrier molecule, the murine monoclonal antibody mAb17-1A. An immunogenic formulation of the SialylTn-mAb17-1A conjugate on alhydrogel, IGN402, with or without additional adjuvants was tested in Rhesus monkeys for tolerability and immunogenicity. A significant antibody response against mAb17-1A antibody was found. Importantly, also a specific immune response against SialylTn carbohydrate and binding to tumor cells was induced. Immunization in the presence of additional adjuvants, such as QS-21, strongly enhanced the immune response against the carbohydrate antigen, and resulted in induction of SialylTn-specific IgG antibodies. Noteworthy, also an induced temporary release of cytokines including IFNγ and IL-2, indicative for T-cell activation, was measured. The data indicate that carrier-induced T-cell help together with strong adjuvant is sufficient for carbohydrate specific class switch induction.