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Targeting TRAIL agonistic receptors for cancer therapy

Carmelo Carlo-Stella1, Cristiana Lavazza, Alberta Locatelli

  • 1Cristina Gandini Medical Oncology Unit, Istituto Nazionale Tumori, Milan, Italy.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|April 18, 2007
PubMed

Insights

Gene therapy using Ad-TRAIL-transduced CD34+ cells shows potent anti-cancer activity. These cells induce apoptosis and vascular disruption, overcoming resistance to TRAIL therapy for improved cancer treatment.

Area of Science:

  • Oncology
  • Gene Therapy
  • Immunology

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows cancer-specific proapoptotic effects.
  • Recombinant TRAIL and TRAIL-receptor antibodies are in clinical trials.
  • Gene therapy with Ad-TRAIL aims to improve TRAIL delivery and efficacy.

Purpose of the Study:

  • To investigate CD34+ cells transduced with Ad-TRAIL (CD34-TRAIL+) as cellular vehicles for TRAIL delivery.
  • To evaluate the anti-tumor activity of CD34-TRAIL+ cells in vitro and in vivo.
  • To understand the mechanisms of tumor cell killing mediated by CD34-TRAIL+ cells.

Main Methods:

  • Transduction of CD34+ cells with Ad-TRAIL.
  • In vitro and in vivo evaluation of CD34-TRAIL+ cell anti-tumor activity.
  • Studies in tumor-bearing nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice.

Main Results:

  • CD34-TRAIL+ cells demonstrated potent tumor-killing activity against various cancer types.
  • Transduced cells were effective against tumor cells resistant to soluble TRAIL.
  • Antitumor effects were mediated by direct apoptosis and indirect vascular disruption.

Conclusions:

  • CD34-TRAIL+ cells are effective cellular vehicles for TRAIL delivery in cancer gene therapy.
  • This approach overcomes limitations of soluble TRAIL and receptor-targeting strategies.
  • Cell and gene therapy holds promise for systemic tumor targeting and enhanced therapeutic delivery.

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