Antibody-Drug-Conjugate Therapy for Hematological Cancers: Matching Cell Biology with Clinical Benefit

摘要

Progress in the development and clinical efficacy of antibody-drug conjugates (ADCs) has attracted the interests of both academic researchers and the industry. The rationale for developing ADCs is based on the inherent non-selectivity of chemotherapy for tumor cells, leading to side effects that can be severe and life threatening. Another major consequence of chemotherapy is the development of drug resistance. For these reasons, targeted drug delivery (TDD) systems are being developed to specifically deliver the cytotoxic drug into the target cell. A variety of carriers that can deliver drugs to the surface or into cancer cells, one of which is the use of monoclonal antibodies, with to date ten ADCs having received FDA approval. This review will focus on the development and clinical application of five ADCs currently approved for the treatment of hematological malignancies. Following a short history that led to their regulatory approval, the review will focus on the important link between the biology of the ADC, the cell surface component targeted by the antibody component, and clinical efficacy and conclude by highlighting newer developments that strengthen this link, so that ADCs can provide long-term clinical benefit to patients with hematological cancers.