In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer

Vivian E. Von Gruenigen, Joseph Santoso, Robert L. Coleman, Carolyn Y. Muller, David Scott Miller, J. Michael Mathis

Research output: Contribution to journalArticle

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Abstract

Objectives. To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation. Study design. An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad- CMV-p53. Nude mice were implanted with an LD100 dose of 1 x 107 cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV- p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 x 108 pfu of Ad-CMV- p53. Results. The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 x 108 pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P = 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice. Conclusions. These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibition in vivo. Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalGynecologic Oncology
Volume69
Issue number3
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

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p53 Genes
Adenoviridae
Genetic Therapy
Ovarian Neoplasms
Nude Mice
Survival
Therapeutics
Neoplasms
Neoplasm Genes
Intraperitoneal Injections
Appointments and Schedules
Safety
Cell Line
Mutation
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynecology

Cite this

Von Gruenigen, V. E., Santoso, J., Coleman, R. L., Muller, C. Y., Miller, D. S., & Mathis, J. M. (1998). In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer. Gynecologic Oncology, 69(3), 197-204. https://doi.org/10.1006/gyno.1998.5010

In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer. / Von Gruenigen, Vivian E.; Santoso, Joseph; Coleman, Robert L.; Muller, Carolyn Y.; Miller, David Scott; Mathis, J. Michael.

In: Gynecologic Oncology, Vol. 69, No. 3, 01.01.1998, p. 197-204.

Research output: Contribution to journalArticle

Von Gruenigen, VE, Santoso, J, Coleman, RL, Muller, CY, Miller, DS & Mathis, JM 1998, 'In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer', Gynecologic Oncology, vol. 69, no. 3, pp. 197-204. https://doi.org/10.1006/gyno.1998.5010
Von Gruenigen, Vivian E. ; Santoso, Joseph ; Coleman, Robert L. ; Muller, Carolyn Y. ; Miller, David Scott ; Mathis, J. Michael. / In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer. In: Gynecologic Oncology. 1998 ; Vol. 69, No. 3. pp. 197-204.
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