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Induction of Tumor Cell Apoptosis by TRAIL Gene Therapy

  • Thomas S. GriffithEmail author
Protocol
Part of the Methods in Molecular Biology™ book series (MIMB, volume 542)

Summary

Members of the tumor necrosis factor (TNF) superfamily influence a variety of immunological functions, including cellular activation, proliferation, and death, upon interaction with a corresponding superfamily of receptors. Whereas interest in the apoptosis-inducing molecules TNF and Fas ligand has peaked because of their participation in events such as autoimmune disorders, activation-induced cell death, immune privilege, and tumor evasion from the immune system, another death-inducing family member, TNF-related apoptosis-inducing ligand (TRAIL), or Apo-2 ligand, has generated excitement because of its unique ability to induce apoptosis in a wide range of transformed cell lines but not in normal tissues. TRAIL is well tolerated when given to healthy animals, and no observable histological or functional changes have been observed in any of the tissues or organs examined. Moreover, multiple injections of soluble TRAIL into mice beginning the day after tumor implantation can significantly suppress the growth of the tumors, with many animals becoming tumor-free. One potential drawback to these findings is that large amounts of soluble TRAIL may be required to inhibit tumor formation, possibly because of the pharmacokinetic profile of soluble TRAIL that indicates that, after intravenous injection, the majority of the protein is rapidly cleared. Increasing the in vivo half-life of recombinant soluble TRAIL or developing an alternative means of delivery may increase the relative tumoricidal activity of TRAIL such that larger, more established tumors could be eradicated as efficiently as smaller tumors. The information presented here describes the production of an adenoviral vector engineered to carry the complementary DNA (cDNA) for murine TRAIL (hTRAIL).

Key Words

Adenovirus apoptosis gene transfer TRAIL tumor 

Notes

Acknowledgments

I thank Dr. Troy K. Kemp, Tamara Kucaba, and Dr. Rebecca L. VanOosten for their technical assistance; and Maria Scheel, Dalyz Ochoa, and the University of Iowa Gene Transfer Vector Core for virus production. This work was supported by the National Cancer Institute (CA109446).

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Urology and the Interdisciplinary Graduate Program in ImmunologyUniversity of IowaIowa CityUSA

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