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 IFNgamma 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.
Kircheis
Ralf
R
Igeneon AG, Immunotherapy of Cancer, Brunnerstrasse 69/3, A-1230 Vienna, Austria. ralf.kircheis@igeneon.com
Vondru
Petra
P
Zinöcker
Irene
I
Häring
Daniela
D
Nechansky
Andreas
A
Loibner
Hans
H
Mudde
Geert C
GC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D011817:Rabbits; D012503:Saponins / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D016207:Cytokines; D007074:Immunoglobulin G; D012503:Saponins; D018074:Vaccines, Conjugate; C055491:sialosyl-Tn antigen; C078785:saponin QA-21V1