Development of an Anti-Muc1 Antibody-Drug Conjugate with Specificity to Target Cancer

Abstract

Ever since Paul Ehrlich, Nobel Prize winner and the founder of chemotherapy, postulated that “magic bullets” can be created and used to fight human disease, scientist have been inspired to develop precise and tailored drugs to target cancer 1. This vision came true with the development of a therapeutic that forms highly specific associations with targeted antigens by Kohler and Milstein in the form of monoclonal antibodies (mAb) 2. Huge advances have been made in the past decade with mAb therapy of cancer to treat many common malignancies with over 206 mAbs studied in clinical trials from 1980 to 2005 2,3. Despite these advances, cancer is still affecting and killing numerous lives every day. The monoclonal antibody therapy for cancer is deemed tailored because it specifically targets antigens expressed on cancer cells. Mucin 1 is a transmembrane mucin that is overexpressed in a number of metastatic epithelial cancers 4,5. Its expression correlates with an aggressive form of disease, poor response to therapy, and poor survival 4. The differences between the antigen in tumor and normal cells in terms of biochemical features, cell distribution, and function 5 provide an opportunity to use antibodies to specifically target and attack Muc1 positive tumor cells. Anti-Muc1 antibodies alone, however, have not proven to be sufficiently cytotoxic to kill tumor cells. Depending on type and stage, current cancer treatments include surgery, radiation, chemotherapy, and immunotherapy. The goal of chemotherapy is to kill the fast-growing cancer cells. However, the drugs are often toxic so that they kill they normal cells in the body, leading to critical side effects. In this project, we aim to combine the high specificity properties of anti-Muc1 antibodies with the highly potent chemotherapeutic agent in order to identify a ‘magic bullet’ immune-based treatment that produces improved efficacy and leads to the specific destruction of tumor-associated Muc1 cancer cells.