Current status of tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R) targeting cancer therapy

Abstract

Monoclonal antibodies have already established a secure position as a very promising strategy for anti-tumor therapeutics. High specificity and high affinity are attractive characteristics of antibodies which make them suitable for clinical applications. Advances in genetic engineering have enabled to generate recombinant antibodies which circumvent the problems of using murine antibodies in human therapy. Immunological effects, specific delivery of antibody conjugated-toxins to target cancer cells, and direct effects through receptor engagement by antibodies have been exploited as mechanisms which generate anti-tumor activity.Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and can induce apoptosis in a wide variety of human cancer cell lines via its interactions with TRAIL receptor 1 (TRAIL-R1) and TRAIL receptor 2 (TRAIL-R2), but does not affect most normal human cells. From the clinical viewpoint, the use of a recombinant soluble form of TRAIL and agonistic antibodies specific for TRAIL-R1 and TRAIL-R2 as anti-tumor agents have been investigated. These promising therapeutic agents are now undergoing clinical investigations.In this review, we summarize the characteristics of recently developed anti-tumor therapeutic antibodies and discuss the current status of therapeutic approaches targeting TRAIL receptors, both by application of TRAIL and by treatment with agonistic monoclonal antibodies. Both these strategies show great promise as therapeutic agents for treatment of cancer patients.