Drugs to Enhance the Therapeutic Potency of Anticancer Antibodies: Antibody-Drug Conjugates as Tumor-Activated Prodrugs

摘要

The development of disease-fighting agents will be increasingly based on information from the genomic analysis of healthy and diseased cells. In cancer this information will eventually lead to the discovery of somatic mutations that led to the generation of tumorigenic cells and the appearance of neoplasias. This will spur the development of treatments directed towards these fundamental tumorigenic mechanisms. Today, genomic analysis of cancer tissues has already yielded biological markers for cancers, such as proteins that are preferentially or exclusively expressed on cancer cells. Monoclonal antibodies can be generated to recognize and specifically bind to these cancer markers. If the markers are expressed on the surface of the cancer cells, monoclonal antibodies administered to a patient will travel to the tumor and accumulate at the tumor through their binding. This can be exploited for the specific delivery of cell-killing drugs in form of covalently linked antibody-drug conjugates. Such antibody-drug conjugates are the most rapid way of converting today's genomic information into specific anti-cancer treatments. The principles guiding the preparation of antibody-drug conjugates, the generation of effective conjugates, and the current development status are discussed.