TRAIL gene therapy: from preclinical development to clinical application.
Numerous studies have investigated the potential use of TNF-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic since its discovery in 1995--because TRAIL is a potent inducer of apoptosis in tumor cells but not in normal cells and tissues. Consequently, a great deal is known about TRAIL/TRAIL receptor expression, the molecular components of TRAIL receptor signaling, and methods of altering tumor cell sensitivity to TRAIL-induced apoptosis. Our laboratory was the first to report the possibility of TRAIL gene transfer therapy as an alternative method of using TRAIL as an antitumor therapy. As with recombinant proteins administered systemically, intratumoral TRAIL gene delivery also has limitations that can restrict its full potential. Translating the preclinical TRAIL studies into the clinic has started, with the hope that TRAIL will exhibit robust tumoricidal activity against human primary tumors in situ with minimal toxic side effects.
Griffith
Thomas S
TS
Department of Urology, University of Iowa, 375 Newton Road, Iowa City, IA 52242, USA. thomas-griffith@uiowa.edu
Stokes
Brittany
B
Kucaba
Tamara A
TA
Earel
James K
JK
VanOosten
Rebecca L
RL
Brincks
Erik L
EL
Norian
Lyse A
LA
D000818:Animals; D002986:Clinical Trials as Topic; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D053221:TNF-Related Apoptosis-Inducing Ligand