Synthesis and Immunological Evaluation of Self-Assembling and Self-Adjuvanting Tricomponent Glycopeptide Cancer-Vaccine Candidates

Abstract

Self-adjuvanting tricomponent vaccines were prepared and assessed for their self-assembly and immunological activity in mouse models. The vaccines each consisted of a peptide or glycopeptide antigen that corresponds to a complete copy of the variable-number tandem repeat (VNTR) of the tumor-associated mucin 1 (MUC1) glycoprotein, the universal T-cell helper peptide epitope PADRE, and the immunoadjuvant Pam₃CysSer. The vaccines were shown to spontaneously self-assemble in water to form isotropic particles varying in size from 17 to 25 nm and elicited robust humoral responses in murine models without the addition of an external adjuvant. The serum antibodies could recognize tumor-associated MUC1 epitopes on the surface of MCF7 breast-cancer cells and B16 melanoma cells, which overexpress this tumor-associated glycoprotein.