Synthetic Vaccines Consisting of Tumor‐Associated MUC1 Glycopeptide Antigens and Bovine Serum Albumin

Abstract

The identification of cell-surface components that occur only on tumor but not on healthy cells is essential for a selective immunological attack on tumor tissue. About 30 years ago, Springer [1] described membrane glycoproteins containing the Thomsen-Friedenreich T antigen and the monosaccharide Tn antigen side chains as tumor-associated antigens on epithelial tumors. These T and Tn glycoproteins were described to be structurally related to the N-terminal region of asialoglycophorin. Based on this structural information, we synthesized a vaccine consisting of N-terminal glycopeptides from asialoglycophorin of M blood group specificity conjugated with bovine serum albumin (BSA) [2] and employed it in the immunization of mice. Although the monoclonal antibody (82-A6) obtained from these experiments showed affinity to epithelial tumor cells, the selectivity for tumor cells was not sufficient.[3] However, the antibody 82-A6 was capable of distinguishing clearly between asialoglycophorin of M and N [*] Dr.

Subsequent Enzymatic Galactosylation and Sialylation Towards Sialylated Thomsen–Friedenreich Antigen Components

“…The disaccharides obtained were sialylated in the final step utilizing trans-sialidase of T. cruzi. Previously sialylated T-antigen determinant structures were efficiently synthesized by Kunz et al [18,19] as well as by Schmidt et al [20] Our enzymatic reaction sequence presented here is straightforward, fast and efficient, affording the desired products in absolute regio-and stereoselectivity.…”

Multivalent, Saccharide‐Functionalized Gold Nanoparticles as Fully Synthetic Analogs of Type A Neisseria meningitidis Antigens

“…[2][3][4][5][6] Systems (molecules or surfaces) that present several copies of identical units are dubbed multivalent. Multivalent interactions [7] are characterized by the simultaneous binding of multiple ligands on one biological entity to multiple receptors on another.…”

Robust immune responses elicited by a fully synthetic three-component vaccine

“…In addition, foreign carrier proteins such as keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA) and the linker that attach the saccharides to the carrier protein can elicit strong B-cell responses, which may lead to the suppression of antibody responses against the carbohydrate epitope 5,6 . It is clear that the successful development of carbohydrate-based cancer vaccines requires novel strategies for the more efficient presentation of tumor-associated carbohydrate epitopes to the immune system, resulting in a more efficient class switch to IgG antibodies [7][8][9][10][11][12][13][14][15][16][17] .…”