Towards the development of peptide mimotopes of carbohydrate antigens as cancer vaccines

Tumor-associated carbohydrate antigens are considered important targets in efforts to develop cancer vaccines. To further enhance vaccine efforts, we are developing peptide mimotopes of tumor-associated carbohydrate antigens that can elicit functional immune responses. Mapping peptide epitopes with anticarbohydrate antibodies can lend to defining structural relationships t hat can go undetected by screening of carbohydrate antigens alone. Here we contrast reactivity patterns for peptides using monoclonal antibodies (MAbs ) directed to the neolactoseries related Lewis Y (LeY) and sialyl-Lewis X ( sLeX) antigen and the GD3/GD2 ganglioside antigen. We observe that represen tative MAbs cross-react with a WRY-containing peptide and that this motif t ype is isolated by the respective monoclonal in peptide phage display scree ning, Primary immunization with multiple antigen peptide preparations with QS-21 adjuvant efficiently elicited cytotoxic IgM antibodies for a murine M eth A fibrosarcoma line expressing sLeX. The cytotoxicity of IgG polyclonal response was found to be as effective as IgM in mediating complement-depen dent cytotoxicity against the Meth A line. These experiments suggest that p eptide mimotopes of the LeY and sLeX tumor-associated carbohydrate antigen and QS-21 adjuvant could be considered as an immunogenic therapeutic vaccin e in carcinoma and melanoma patients in the minimal residual disease settin g.