Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
A systemic anticancer chemotherapy induces a variety of side effects by affecting normal cells. Therefore, to reduce side effects and increase the efficacy, the development of DDS techniques and drugs aimed at accumulation in cancer tissues have been promoted. Antibody-Drug Conjugates (ADCs) composed of cytotoxic drugs with severe side effects and monoclonal antibodies with less drug efficacy instead of fewer side effects, which directly binds to the target antigen and delivers the drug to cancer cells leading to selectively and effectively kill cancer cells. By expanding the therapeutic dose range between the minimum effective dose and the maximum tolerated dose, it is expected to exert a strong anticancer effect compared with generally used chemotherapeutic agents. Multiple ADCs have already been launched, and in addition, many ADCs for advanced cancer are being developed in clinical trials. Trastuzumab deruxtecan (T-DXd, DS-8201), developed by Daiichi Sankyo Co., Ltd., is an ADC that binds the exatecan derivative DXd, a DNA topoisomerase I inhibitor, to anti HER2 antibody via a cleavable linker in tumor cells. Its main features are high uniformity with a high drug-antibody ratio of 8 on average, strong drug efficacy to heterogeneous tumors due to bystander effects being independent on the target molecule, and high stability in circulation enabling a wide therapeutic window. The technical features and efficacy of T-DXd will be summarized and its toxicological profile including interstitial lung disease (ILD) will be discussed both clinically and non-clinically.
