Potent antibody drug conjugates for cancer therapy.
Significant progress has been made in the past few years in the area of antibody drug conjugates (ADCs) for the selective delivery of cytotoxic drugs to tumors. Early work in this field incorporated clinically approved drugs and mouse monoclonal antibodies (mAbs), which had modest activities, and were generally immunogenic. The results of these studies prompted investigation that led to the identity of several key parameters that influenced activity and tolerability. These included the antigen target, the use of non-immunogenic mAb carriers, the incorporation of highly potent drugs and novel conditionally stable linker technologies, and the specific methods used to attach drugs to mAbs. As a result of these investigations, new agents with pronounced clinical activities have been developed. These include SGN-35, an ADC directed against the CD30-positive malignancies such as Hodgkin's disease and anaplastic large cell lymphoma, and trastuzumab-DM1 which has shown activity in metastatic breast carcinoma. This review details many of the technological advancements, and provides examples of promising ADCs that are currently in clinical trials.
Senter
Peter D
PD
Seattle Genetics, Inc., 21823 30th Dr. SE, Bothell, WA 98021, United States. psenter@seagen.com
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D003603:Cytotoxins / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D003603:Cytotoxins; D018796:Immunoconjugates