Clinical targeting of the TNF and TNFR superfamilies

The clinical success of inhibitors of tumour necrosis factor (TNF) in the treatment of autoimmune diseases has generated interest in the therapeutic potential of targeting other members of the TNF superfamily (TNFSF) of cytokines and their receptors. Here, Croft and colleagues review the current developmental status of biologics targeting these molecules in a range of disorders, highlighting key challenges and emerging therapeutic targets. Inhibitors of tumour necrosis factor (TNF) are among the most successful protein-based drugs (biologics) and have proven to be clinically efficacious at reducing inflammation associated with several autoimmune diseases. As a result, attention is focusing on the therapeutic potential of additional members of the TNF superfamily of structurally related cytokines. Many of these TNF-related cytokines or their cognate receptors are now in preclinical or clinical development as possible targets for modulating inflammatory diseases and cancer as well as other indications. This Review focuses on the biologics that are currently in clinical trials for immune-related diseases and other syndromes, discusses the successes and failures to date as well as the expanding therapeutic potential of modulating the activity of this superfamily of molecules.