Challenges and opportunities to develop enediyne natural products as payloads for antibody-drug conjugates. (12th January 2021)

• Record Type: Journal Article
• Authors: Adhikari, Ajeeth; Shen, Ben; Rader, Christoph
• Is Part Of: Antibody therapeutics. Volume 4:Number 1(2021)
• Page Start: 1
• Page End: 15
• Publication Date: 2021-01-12
• Subjects: antibody-drug conjugates -- payloads -- enediyne natural products -- gemtuzumab ozogamicin -- inotuzumab ozogamicin -- anthraquinone-fused enediynes; Immunoglobulins -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Therapeutic use -- Periodicals; Immunotechnology -- Periodicals; 616.0798
• DOI: 10.1093/abt/tbab001
• Languages: English
• ISSNs: 2516-4236

Abstract

Abstract: Calicheamicin, the payload of the antibody-drug-conjugates (ADCs) gemtuzumab ozogamicin (Mylotarg®) and inotuzumab ozogamicin (Besponsa®), belongs to the class of enediyne natural products. Since the isolation and structural determination of the neocarzinostatin chromophore in 1985, the enediynes have attracted considerable attention for their value as DNA damaging agents in cancer chemotherapy. Due to their non-discriminatory cytotoxicity towards both cancer and healthy cells, the clinical utilization of enediyne natural products relies on conjugation to an appropriate delivery system, such as an antibody. Here, we review the current landscape of enediynes as payloads of first-generation and next-generation ADCs.