Antibody–drug conjugates: What drives their progress?. Issue 10 (October 2022)

• Record Type: Journal Article
• Authors: Pander, Giulia; Uhl, Philipp; Kühl, Nikos; Haberkorn, Uwe; Anderl, Jan; Mier, Walter
• Is Part Of: Drug discovery today. Volume 27:Issue 10(2022)
• Publication Date: 2022-10
• Subjects: Tumor targeting -- Monoclonal antibodies -- Antibody–drug conjugates -- Chemotherapy -- Drug delivery -- Toxins -- Drug resistance; Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2022.06.011
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: In ADCs, small molecule toxins are tethered to monoclonal antibodies. A significant increase in knowledge enables optimization of this class of drugs. Key aspects: formulation, dosing scheme, internalization rates and linker stability. Comprehensive analysis of the mechanisms underlying the design of ADCs. Insight into mechanisms of resistance and developments to overcome resistance. Abstract : Antibody–drug conjugates (ADCs) are on the brink of widespread use for the targeted treatment of cancer. ADCs manage the toxicity of drugs with unacceptable narrow therapeutic windows by guiding highly toxic compounds to the target cells, thereby sparing healthy cells. In this review, we describe approved ADCs and discuss their modes of action, together with medicinal chemical aspects, to evaluate the potential for improvement and to combat tumor-acquired resistance. A recent research focus has centered on the stimulation of immune responses to induce immunogenic cell death and the influence on the tumor microenvironment to enhance bystander effects.