Eliminating established tumor in nu/nu nude mice by a tumor necrosis factor-α-related apoptosis-inducing ligand-armed oncolytic adenovirus

Fengqin Dong, Li Wang, John J. Davis, Wenxian Hu, Lidong Zhang, Wei Guo, Fuminori Teranishi, Lin Ji, Bingliang Fang

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Purpose: The tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) and oncolytic viruses have recently been investigated extensively for cancer therapy. However, preclinical and clinical studies have revealed that their clinical application is hampered by either weak anticancer activity or systemic toxicity. We examined whether the weaknesses of the two strategies can be overcome by integrating the TRAIL gene into an oncolytic vector. Experimental Design: We constructed a TRAIL-expressing oncolytic adenovector designated as Ad/TRAIL-E1. The expression of both the TRAIL and viral E1A genes is under the control of a synthetic promoter consisting of sequences from the human telomerase reverse transcriptase promoter and a minimal cytomegalovirus early promoter. The transgene expression, apoptosis induction, viral replication, antitumor activity, and toxicity of Ad/TRAIL-E1 were determined in vitro and in vivo in comparison with control vectors. Results: Ad/TRAIL-E1 elicited enhanced viral replication and/or stronger oncolytic effect in vitro in various human cancer cell lines than a TRAIL-expressing, replication-defective adenovector or an oncolytic adenovector - expressing green fluorescent protein. Intralesional administration of Ad/TRAIL-E1 eliminated all s.c. xenograft tumors established from a human non-small cell lung cancer cell line, H1299, on nu/nu nude mice, resulting in long-term, tumor-free survival. Furthermore, we found no treatment-related toxicity. Conclusions: Viral replication and antitumor activity of oncolytic adenovirus can be enhanced by the TRAIL gene and Ad/TRAIL-E1 could become a potent therapeutic agent for cancer therapy.

Original languageEnglish
Pages (from-to)5224-5230
Number of pages7
JournalClinical Cancer Research
Volume12
Issue number17
DOIs
Publication statusPublished - Sep 1 2006
Externally publishedYes

Fingerprint

Adenoviridae
Nude Mice
Tumor Necrosis Factor-alpha
Apoptosis
Ligands
Neoplasms
Oncolytic Viruses
Cell Line
Viral Genes
Green Fluorescent Proteins
Cytomegalovirus
Transgenes
Heterografts
Non-Small Cell Lung Carcinoma
Genes
Research Design
Therapeutics
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Eliminating established tumor in nu/nu nude mice by a tumor necrosis factor-α-related apoptosis-inducing ligand-armed oncolytic adenovirus. / Dong, Fengqin; Wang, Li; Davis, John J.; Hu, Wenxian; Zhang, Lidong; Guo, Wei; Teranishi, Fuminori; Ji, Lin; Fang, Bingliang.

In: Clinical Cancer Research, Vol. 12, No. 17, 01.09.2006, p. 5224-5230.

Research output: Contribution to journalArticle

Dong, Fengqin ; Wang, Li ; Davis, John J. ; Hu, Wenxian ; Zhang, Lidong ; Guo, Wei ; Teranishi, Fuminori ; Ji, Lin ; Fang, Bingliang. / Eliminating established tumor in nu/nu nude mice by a tumor necrosis factor-α-related apoptosis-inducing ligand-armed oncolytic adenovirus. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 17. pp. 5224-5230.
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AU - Hu, Wenxian

AU - Zhang, Lidong

AU - Guo, Wei

AU - Teranishi, Fuminori

AU - Ji, Lin

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