Project 466634

Monoclonal antibodies (mAbs) have revolutionized cancer therapy, and trastuzumab has revolutionized HER2+ breast cancer. Increasingly, antibody drug conjugates such as trastuzumab emtansine play an important role in the treatment of relapsed disease. Positron emitting radioisotopes can be used as an alternative payload that can be carried by mAbs, for non-invasive cancer localization and confirmation of target expression by positron emission tomography (PET). In addition, therapeutic radioisotopes can deliver and concentrate radiation to treat metastatic sites. However, directly labeled mAbs with long-living radioisotopes such as Zr-89 clear slowly from the body, exposing the bone marrow and other organs to unnecessary radiation due to slow clearance.Researchers have recently developed pretargeted radioimmunotherapy to improve contrast for imaging and efficacy for therapy. In this approach, a modified mAb is injected and allowed to circulate, bind to cancer cells, and clear from the blood over a few days. Then, a fast clearing small molecule that specifically recognises the antibody is administered, clearing within minutes, with the goal of targeting cancer cells specifically coated with the antibody.The goal is to develop nucleic acids such as DNA to specifically recognize mAbs that have been preinjected to target tumor cells. They act as means to conjugate antibodies coated with one strand of DNA, with a small strand of complementary nucleic acids attached to a radioactive isotope. The radioactive DNA binds tightly to the complementary strand located on the antibody, using the established antibody Trastuzumab in breast cancer as a proof-of-concept. Confirmation of tumor localization will be used as the first evidence to preview the effectiveness of this approach.