Antibody drug-conjugates targeting the tumor vasculature: Current and future developments.
Reducing the blood supply of tumors is one modality to combat cancer. Monoclonal antibodies are now established as a key therapeutic approach for a range of diseases. Owing to the ability of antibodies to selectively target endothelial cells within the tumor vasculature, vascular targeting programs have become a mainstay in oncology drug development. However, the antitumor activity of single agent administration of conventional anti-angiogenic compounds is limited and the improvements in patient survival are most prominent in combinations with chemotherapy. Furthermore, prolonged treatment with conventional anti-angiogenic drugs is associated with toxicity and drug resistance. These circumstances provide a strong rationale for novel approaches to enhance the efficacy of mAbs targeting tumor vasculature such as antibody-drug conjugates (ADCs).Here, we review trends in the development of ADCs targeting tumor vasculature with the aim of informing future research and development of this class of therapeutics.
Gerber
Hans-Peter
HP
Department of Pre-Clinical Therapeutics, Seattle Genetics, Inc., Bothell, WA 98021, USA.
Senter
Peter D
PD
Grewal
Iqbal S
IS
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000941:Antigens / Q000276:immunology; D001808:Blood Vessels / Q000276:immunology; D015195:Drug Design; D004351:Drug Resistance; D006801:Humans; D007167:Immunotherapy / Q000639:trends*; D000922:Immunotoxins / Q000627:therapeutic use*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*
D020533:Angiogenesis Inhibitors; D000941:Antigens; D000922:Immunotoxins