On the power of chemical synthesis: Immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines

• DOI: 10.1073/pnas.202427599
• Publication Date: 2002-10-15T16:43:03Z
• Authors: Govindaswami Ragu...; Don M. Coltart; Lawrence J. Williams; Fusataka Koide; Ella Kagan; Jennifer Allen; Christina Harris; Peter W. Glunz; Philip O. Livingston; Samuel J. Danishe...
• Keywords: Hemocyanin; Cancer vaccine

Synthetic carbohydrate cancer vaccines have been shown to stimulate antibody-based immune responses in both preclinical and clinical settings. The antibodies observed react vitro with the corresponding natural antigens expressed on surface of tumor cells, are able mediate complement-dependent and/or antibody-dependent cell-mediated cytotoxicity. Furthermore, these proven be safe when administered patients. Until recently, only monovalent antigen constructs had prepared evaluated. Advances total synthesis now enabled preparation multivalent vaccine constructs, which contain several different tumor-associated antigens. Such could, principle, serve as superior mimics cell and, hence, potent vaccines. Here we report ELISA-based evaluation a TF–Le y –Tn bearing construct (compound 3) native mucin glycopeptide architecture Globo-H–Le 4) nonnative structure. Mice were immunized one or other free glycopeptides keyhole lymphet hemocyanin conjugates. Either QS-21 related GPI-0100 coadministered adjuvants. Both conjugates induced IgM IgG against each antigen, however, mucin-based was less antigenic than unnatural construct. adjuvants, although related, proved significantly different, that consistently higher titers QS-21. presence multiple glycans did not appear suppress response any constituent Compound 4, more two also examined by fluorescence activated sorter analysis. Significantly, from studies it stimulated compound 4 reacted cells known selectively express individual results demonstrate single potential multifaceted response.