In vivo surgical resection plus adjuvant gene therapy in the treatment of mammary and prostate cancer

Steven W. Sukin, Madhu Chhikara, Xiaohong Zhu, Gustavo Ayala, Laura K. Aguilar, E. O'Brian Smith, Brian J. Miles, Timothy C. Thompson, Dov Kadmon, Estuardo Aguilar-Cordova

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Adenoviral-mediated gene therapy delivery, combining the herpes simplex virus thymidine kinase gene (Ad-tk) with gancyclovir, has been evaluated as a treatment modality for numerous tumors in the laboratory and in the clinics. As a single modality, gene therapy has shown some promising local and systemic results but no curative success. Surgery is the standard of care for many solid tumors. However, minor residual tumor following surgical resection can lead to local recurrence, and surgery is neither efficient nor plausible for metastatic disease. In this study, two tumor models were used to evaluate the effects of Ad-tk gene therapy as an adjuvant to surgery. Subcutaneous mammary- and prostate-derived tumors were produced in syngeneic mice. To evaluate systemic effects, tumor cells were injected intravenously, with subsequent formation of lung nodules. The subcutaneous tumors were surgically resected and the tumor bed was bathed with saline or Ad-tk. The animals were evaluated for toxicity, local tumor recurrence, survival, and lung nodule formation. No evidence of additional toxicity was observed. In the less aggressive mammary model, the time to recurrence was increased from 11.7 (±1.0) days to 22.7 (±5.5) days. In the prostate model, recurrence went from a mean of 17.3 (±5.6) to 22.6 (±6.8) days. Survival was also improved from a mean of 19.7 (±1.1) to 32.3 (±4.8) and 26.1 (±5.0) to 34.1 (±6.1) days in the mammary and prostate models, respectively. Evidence of systemic benefits from the use of adjuvant Ad-tk therapy was demonstrated by a significant reduction in lung nodules from a mean of 17 to 3.5. These results suggest that Ad-tk gene therapy may be a useful adjuvant for patients undergoing surgery for treatment of cancer.

Original languageEnglish (US)
Pages (from-to)500-506
Number of pages7
JournalMolecular Therapy
Volume3
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Gene therapy
  • Mammary
  • Prostate

ASJC Scopus subject areas

  • Molecular Biology

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