A probasin promoter, conditionally replicating adenovirus that expresses the sodium iodide symporter (NIS) for radiovirotherapy of prostate cancer

M. A. Trujillo, M. J. Oneal, S. McDonough, R. Qin, J. C. Morris

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The sodium iodide symporter (NIS) directs the uptake and concentration of iodide in thyroid cells. We have extended the use of NIS-mediated radioiodine therapy to other types of cancer, we transferred and expressed the NIS gene into prostate, colon and breast cancer cells using adenoviral vectors. To improve vector efficiency we have developed a conditionally replicating adenovirus (CRAd) in which the E1a gene is driven by the prostate-specific promoter, Probasin and the cassette RSV promoter human NIScDNA-bGH polyA replaces the E3 region (CRAd Ad5PB-RSV-NIS). In vitro infection of the prostate cancer cell line LnCaP resulted in virus replication, cytolysis and release of infective viral particles. Conversely, the prostate cancer cell line PC-3 (androgen receptor negative) and the pancreatic cancer cell line Panc-1 were refractory to the viral cytopathic effect and did not support viral replication. Radioiodine uptake was readily measurable in LnCaP cells infected with Ad5PB-RSV-NIS 24 h post-infection, confirming NIS expression. In vivo, LnCaP tumor xenografts in nude-mice injected intratumorally with Ad5PB-RSV-NIS CRAd expressed NIS actively as evidenced by 99 Tc uptake and imaging. Administration of therapeutic 131 I after virus injection significantly increased survival probability in mice carrying xenografted LnCaP tumors compared with virotherapy alone. These data indicate that Ad5PB-RSV-NIS replication is stringently restricted to androgen-positive prostate cancer cells and results in effective NIS expression and uptake of radioiodine. This construct may allow multimodal therapy, combining cytolytic virotherapy with radioiodine treatment, to be developed as a novel treatment for prostate cancer.

Original languageEnglish (US)
Pages (from-to)1325-1332
Number of pages8
JournalGene Therapy
Volume17
Issue number11
DOIs
StatePublished - Nov 2010

Fingerprint

Adenoviridae
Prostatic Neoplasms
Cell Line
Viral Cytopathogenic Effect
Virus Release
Therapeutics
Neoplasms
Androgen Receptors
Iodides
Virus Replication
Infection
Pancreatic Neoplasms
Heterografts
Nude Mice
Virion
Colonic Neoplasms
Androgens
Genes
Prostate
Thyroid Gland

Keywords

  • adenovirus
  • gene therapy
  • probasin
  • prostate cancer
  • sodium iodide symporter
  • virotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

A probasin promoter, conditionally replicating adenovirus that expresses the sodium iodide symporter (NIS) for radiovirotherapy of prostate cancer. / Trujillo, M. A.; Oneal, M. J.; McDonough, S.; Qin, R.; Morris, J. C.

In: Gene Therapy, Vol. 17, No. 11, 11.2010, p. 1325-1332.

Research output: Contribution to journalArticle

Trujillo, M. A. ; Oneal, M. J. ; McDonough, S. ; Qin, R. ; Morris, J. C. / A probasin promoter, conditionally replicating adenovirus that expresses the sodium iodide symporter (NIS) for radiovirotherapy of prostate cancer. In: Gene Therapy. 2010 ; Vol. 17, No. 11. pp. 1325-1332.
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