Related Experiment Video
Updated: Aug 13, 2026
Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System
Published on: July 30, 2018
Suppression of tumor growth following intralesional therapy with TRAIL recombinant adenovirus
1Department of Urology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242-1089, USA. thomas-griffith@uiowa.edu
Abstract:
TRAIL is a member of the tumor necrosis factor superfamily that induces apoptosis in a variety of tumor cell types both in vitro and in vivo, while demonstrating minimal cytotoxicity toward normal tissues. One disadvantage to previous in vivo protocols was the need for large quantities of TRAIL to suppress tumor growth. Here we engineered a replication-deficient adenovirus to encode human TNFSF10 (Ad5-TRAIL) as an alternative to recombinant, soluble TRAIL protein. The results show that TRAIL-sensitive prostate tumor cell targets infected with Ad5-TRAIL undergo apoptosis through the production and expression of TRAIL protein. This activity was limited to TRAIL-sensitive tumor cells, as normal prostate epithelial cells were not killed by Ad5-TRAIL. Furthermore, in vivo administration of Ad5-TRAIL at the site of tumor implantation suppressed the outgrowth of human prostate tumor xenografts in SCID mice. Histologic examination of prostate tumors treated locally with Ad5-TRAIL revealed areas of apoptosis within 24 hours of injection. These results further define Ad5-TRAIL as a novel anti-tumor therapeutic and demonstrate its potential use as a means for treating prostate tumors, as well as other solid tumors, in vivo.
Insights
Engineered adenovirus (Ad5-TRAIL) delivers tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to effectively induce apoptosis in prostate tumor cells. This novel therapeutic suppressed tumor growth in vivo with minimal impact on normal tissues.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but requires high doses for in vivo efficacy.
- Previous methods using soluble TRAIL protein faced limitations in achieving sufficient therapeutic concentrations in vivo.
Purpose of the Study:
- To engineer a replication-deficient adenovirus encoding human TNFSF10 (Ad5-TRAIL) as an alternative to recombinant TRAIL protein.
- To evaluate the efficacy and specificity of Ad5-TRAIL in inducing apoptosis in TRAIL-sensitive prostate tumor cells and suppressing tumor growth in vivo.
Main Methods:
- Adenovirus vector construction to encode human TNFSF10 (TRAIL).
- In vitro assessment of Ad5-TRAIL-induced apoptosis in prostate tumor cells and normal prostate epithelial cells.
- In vivo administration of Ad5-TRAIL at tumor implantation sites in SCID mice xenograft models.
- Histological analysis of tumor tissues post-treatment.
Main Results:
- Ad5-TRAIL infection induced apoptosis in TRAIL-sensitive prostate tumor cells via TRAIL protein production and expression.
- Normal prostate epithelial cells remained unaffected by Ad5-TRAIL, demonstrating specificity.
- Local administration of Ad5-TRAIL suppressed the outgrowth of human prostate tumor xenografts in SCID mice.
- Apoptotic changes were observed in prostate tumors within 24 hours of Ad5-TRAIL injection.
Conclusions:
- Ad5-TRAIL is a novel anti-tumor therapeutic agent.
- Ad5-TRAIL demonstrates potential for treating prostate tumors and other solid tumors in vivo.
- Adenovirus-mediated delivery of TRAIL offers an effective alternative to recombinant protein for cancer therapy.
