Synthesis and Immunological Evaluation of a Multicomponent Cancer Vaccine Candidate Containing a Long MUC1 Glycopeptide

Abstract

A fully synthetic MUC1-based cancer vaccine has been designed and chemically synthesized that contains an endogenous helper T-epitope (MHC class II epitope). The vaccine elicited robust IgG titers that could neutralize cancer cells by antibody-dependent cell-mediated cytotoxicity (ADCC). It also activated cytotoxic T-lymphocytes and collectively the immunological data demonstrate engagement of helper T-cells in immune activation. A synthetic methodology was developed for a penta-glycosylated MUC1 glycopeptide and anti-sera of mice immunized by the new vaccine recognized such a structure. Previous reported fully synthetic MUC-1 based cancer vaccines that elicited potent immune responses employed exogenous helper T-epitopes derived from microbes. It is the expectation that the use of the newly identified endogenous helper T-epitope will be more attractive because it will activate cognate CD4+ T-cells that will provide critical tumor-specific help intra-tumorally during the effector stage of tumor rejection and will aid in the generation of sustained immunological memory.