The extracellular domain of mucin 1 (MUC1) is an attractive target for the development of therapeutic cancer vaccines.1 In fact, the tumor-associated form of MUC1 (TA-MUC1) is markedly underglycoslyated and displays new peptide and carbohydrate epitopes. Moreover, TA-MUC1 is overexpressed on a large variety of cancer cells. Thus, if properly instructed with a vaccine, the immune system may be able to recognize cancer cells based on these features killing them selectively. Although a number of vaccine design strategies have been pursued, successful anticancer vaccines are yet to be obtained. We are developing cancer vaccines based on PEGylated gold nanoparticles (AuNPs) carrying glycopeptide antigens.2 In this contribution we describe the design, preparation and implementation of novel AuNP-based vaccine candidates carrying non-natural glycopeptides as TA-MUC1 antigen mimics. These antigen mimics present a single O/S substitution at the glycosidic linkage of a glycosylated amino acid to improve bioavailability. We have immobilized these TA-MUC1 antigen mimics on AuNPs and tested them as immunogen formulation in mice.3 A significant humoral immune response is obtained in the absence of any additional adjuvant. Moreover, the mice antisera stain with high selectivity cancer cells in biopsies of breast cancer patients demonstrating that the antibodies elicited against the antigen mimic recognize the naturally occurring antigen in its physiological context. Clinically, the exploitation of tumor-associated antigen mimics may contribute to the development of cancer vaccines and the improvement of cancer diagnosis based on antibodies.

Design and implementation of gold-nanoparticle formulations as MUC1-directed cancer vaccines

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.