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...

Full description

Saved in:
Bibliographic Details
Published in:Bioconjugate chemistry 2005-11, Vol.16 (6), p.1519-1528
Main Authors: Kircheis, Ralf, Vondru, Petra, Nechansky, Andreas, Ohler, Renate, Loibner, Hans, Himmler, Gottfried, Mudde, Geert C
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - administration & dosage
Antibody Specificity
Antigens, Tumor-Associated, Carbohydrate - administration & dosage
Antigens, Tumor-Associated, Carbohydrate - immunology
Biochemistry
Cancer Vaccines - immunology
Carbohydrates
Epitopes
Gene expression
Immunoconjugates - administration & dosage
Immunoglobulin G
Immunologic Memory
Immunology
Macaca mulatta
Tumors
Vaccines
Vaccines, Conjugate - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc050157m