Antitumor activity of human CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand

Hum Gene Ther. 2006 Dec;17(12):1225-40. doi: 10.1089/hum.2006.17.1225.


Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in a variety of transformed cells while sparing normal cells. To enhance the therapeutic index of soluble (s)TRAIL, we used CD34+ cells transduced with a replication-deficient adenovirus encoding the human TRAIL gene (CD34-TRAIL+) for the systemic delivery of membrane-bound (m)TRAIL to lymphoid tumors. CD34-TRAIL+ cells were evaluated for their activity in vitro and in vivo in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenografted with sTRAIL-sensitive and -resistant tumors. In vitro, coculturing CD34-TRAIL+ cells with sTRAIL-sensitive or -resistant lymphoma cell lines induced significant levels of caspase-dependent tumor cell death. In vivo, CD34-TRAIL+ cells significantly increased the survival of NOD/SCID mice bearing sTRAIL-sensitive or -resistant lymphoid tumors at an early or advanced stage of disease. No obvious toxicity was observed on administration of CD34-TRAIL+ cells. Histological analysis revealed high-level expression of the agonistic receptor TRAIL-R2 by tumor endothelial cells, and efficient tumor homing of transduced cells. Injection of CD34-TRAIL+ cells resulted in extensive damage of tumor vasculature followed by hemorrhagic necrosis exhibiting a perivascular distribution. These results show that CD34-TRAIL+ cells might be an efficient vehicle for mTRAIL delivery to tumors, where they exert a potent antitumor effect possibly mediated by both direct tumor cell killing and indirect vascular-disrupting mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antigens, CD34 / metabolism*
  • Female
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods*
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Transplantation
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*
  • TNF-Related Apoptosis-Inducing Ligand / genetics*
  • Transduction, Genetic
  • Transplantation, Heterologous


  • Antigens, CD34
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human