TNF-related apoptosis-inducing ligand as a therapeutic agent in autoimmunity and cancer.
Recombinant, soluble TNF-related apoptosis-inducing ligand (TRAIL) is currently being developed as a promising natural immune molecule for trial in cancer patients because it selectively induces apoptosis in transformed or stressed cells but not in most normal cells. In cancer patients, phase 1 and 2 clinical trials using agonistic mAbs that engage the human TRAIL receptors DR4 and DR5 have also provided encouraging results. It is now evident that TRAIL suppresses autoimmune disease in various experimental animal models, suggesting that the therapeutic value of recombinant TRAIL and agonistic DR4 and DR5 mAbs might also extend to the suppression of autoimmune disease. This review provides an insight into our current understanding of the role(s) of TRAIL in disease, with a specific focus on cancer and autoimmunity. We also emphasize biological agents and drugs that sensitize tumour cells to TRAIL-mediated apoptosis and discuss the potential molecular basis for their sensitization.
Cretney
Erika
E
Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Shanker
Anil
A
Yagita
Hideo
H
Smyth
Mark J
MJ
Sayers
Thomas J
TJ
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology / Q000627:therapeutic use*; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha