Development of active specific immunotherapeutic agents based on cancer-associated mucins.

Abstract

As a result of aberrant glycosylation, cancer-associated mucins expose to the immune system certain carbohydrate, peptide, and possibly glycopeptide epitopes that are not exposed on the normal mucins. This provides the basis for our development of synthetic carbohydrate, peptide, and glycopeptide-based ASI agents corresponding to the cancer-associated mucin epitopes. Our studies on ASI formulations based on carbohydrate structures such as TF and STn have demonstrated their ability to induce immune response relevant to the native epitopes on the cancer cells in animal models and in cancer patients. Further, such immune responses were able to mediate cancer rejection in an animal model. Similar studies on peptide epitopes of a cancer-associated mucin, MUC1, have also shown the ability of the synthetic antigen to induce anticancer immune responses in an animal model. Ongoing studies on the carbohydrate and peptide epitopes would allow us to define the most important target structures on cancer-associated mucins that can selectively stimulate cancer-specific immune responses. Our long-term goal is to develop multiepitopic glycopeptide ASI formulations capable of stimulating strong CMI responses against common carcinomas.