Intratumor murine interleukin-12 gene therapy suppressed the growth of local and distant Ewing's sarcoma.
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 beta-galactosidase (Ad.beta-gal) or adenovirus murine IL-12 (Ad.mIL-12) (2 x 10(9) 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.beta-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.beta-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.beta-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.
Jia
S-F
SF
Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Duan
X
X
Worth
L L
LL
Guan
H
H
Kleinerman
E S
ES
D000818:Animals; D001483:Base Sequence; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
D017931:DNA Primers; D018664:Interleukin-12