1. ¹Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
2. ²Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Dr ES Kleinerman, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 87, Houston, TX 77030, USA. E-mail: ekleiner@mdanderson.org

Received 29 September 2005; Revised 16 March 2006; Accepted 22 April 2006; Published online 9 June 2006.

Abstract

We evaluated the effect of interleukin-12 (IL-12) gene therapy using an Ewing's sarcoma animal model in T-cell-deficient nude mice. Subcutaneous injection of TC71 cells resulted in tumor development by day 5. Mice were treated with a single intratumor injection of adenovirus -galactosidase (Ad.-gal) or adenovirus murine IL-12 (Ad.mIL-12) (2 10⁹ PFU) and killed 1–7 days later. Reverse transcriptase-polymerase chain reaction analysis of tumor tissue demonstrated peak expression of IL-12 p35 and p40 at 48 h, which persisted up to 7 days. For in vivo therapy, mice received intratumor Ad.-gal or Ad.mIL-12 twice weekly for 2.5 weeks starting on day 6. Ad.mIL-12-treated tumors were significantly smaller (median volume, 19.7 mm³; range, 3.41–159.5 mm³) than Ad.-gal-treated tumors (median volume, 3214.9 mm³; range 1679.9–5909.8 mm³, P<0.003) on day 31. The weight of Ad.mIL-12-treated tumors was also lighter than the Ad.-gal-treated tumors (median, 2 mg; range, 1–5 mg versus median, 1960 mg; range 1640–5230 mg, P<0.01). Ad.mIL-12 therapy significantly prolonged the survival time and also inhibited the growth of an untreated tumor on the contralateral side. Immunohistochemistry analysis of the IL-12-treated tumors demonstrated IL-12 expression with increased Fas, Fas ligand and tumor cell apoptosis. CD31 and vascular endothelial growth factor expression were decreased. These data suggest that IL-12 gene therapy may be useful in the treatment of Ewing's sarcoma.