Antibody-drug conjugates for cancer therapy.
The antibody-drug conjugate (ADC) concept is to use an antibody to deliver a cytotoxic drug selectively to a target such as a tumor-associated antigen. Such conjugates represent a broadly applicable approach to enhance the antitumor activity of antibodies and improve the tumor-to-normal tissue selectivity of chemotherapy. Critical parameters for ADC development include target antigen selection, conjugate internalization by tumor cells, drug potency and stability of the linker between drug and antibody. Other important considerations include the conjugation methods, drug-to-antibody ratio, and the effects of drug conjugation on antibody properties. Highly potent drugs with more stable linkers have been attached to a new generation of antibodies to create conjugates with pronounced antitumor activities in preclinical studies and encouraging results in early stage clinical trials. This review details these advances, discusses some of the remaining challenges, and overviews ADCs currently in clinical trials for cancer therapy.
Carter
Paul J
PJ
Seattle Genetics, Inc., Bothell, Washington 98021, USA. pcarter@seagen.com
Senter
Peter D
PD
D000617:Aminoglycosides / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000378:metabolism*; D000079982:Gemtuzumab; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000628:therapy; D011961:Receptors, Fc / Q000378:metabolism
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; D007155:Immunologic Factors; D000922:Immunotoxins; D011961:Receptors, Fc; D000079982:Gemtuzumab