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TNF-related apoptosis-inducing ligand as a therapeutic agent in autoimmunity and cancer

Erika Cretney1, Anil Shanker, Hideo Yagita

  • 1Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Immunology and Cell Biology
|January 13, 2006
PubMed

Insights

Recombinant TNF-related apoptosis-inducing ligand (TRAIL) shows promise for cancer therapy by selectively inducing apoptosis in cancer cells. Its potential therapeutic value also extends to suppressing autoimmune diseases.

Area of Science:

  • Immunology
  • Oncology
  • Rheumatology

Background:

  • Recombinant, soluble TNF-related apoptosis-inducing ligand (TRAIL) is a promising immune molecule for cancer therapy.
  • TRAIL selectively induces apoptosis in transformed or stressed cells, sparing most normal cells.
  • Clinical trials with agonistic monoclonal antibodies (mAbs) targeting TRAIL receptors DR4 and DR5 show encouraging results in cancer patients.

Purpose of the Study:

  • To review the current understanding of TRAIL's role in cancer and autoimmune diseases.
  • To explore the therapeutic potential of recombinant TRAIL and DR4/DR5 agonistic mAbs in autoimmunity.
  • To identify biological agents and drugs that sensitize tumor cells to TRAIL-mediated apoptosis.

Main Methods:

  • Literature review focusing on TRAIL's function in cancer and autoimmunity.
  • Analysis of preclinical animal models and clinical trial data for TRAIL-based therapies.
  • Examination of molecular mechanisms underlying TRAIL sensitization in tumor cells.

Main Results:

  • TRAIL demonstrates selective apoptosis induction in cancer cells, supporting its use in oncology.
  • TRAIL has shown efficacy in suppressing autoimmune diseases in experimental animal models.
  • Various agents can sensitize tumor cells to TRAIL-mediated apoptosis, enhancing therapeutic strategies.

Conclusions:

  • Recombinant TRAIL and DR4/DR5 agonistic mAbs hold therapeutic potential for both cancer and autoimmune diseases.
  • Understanding TRAIL sensitization mechanisms is crucial for optimizing cancer treatment.
  • TRAIL represents a significant target for novel immunotherapies in oncology and rheumatology.

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