Inhibition of established subcutaneous and metastatic murine tumors by intramuscular electroporation of the interleukin-12 gene.
In vivo electroporation (EP) of the murine interleukin-12 (IL-12) gene in an expression plasmid (pIL-12) was evaluated for antitumor activity. EP transfer of pIL-12 into mouse quadriceps muscles elicited significant levels of serum IL-12 and interferon-gamma. Intramuscular EP of pIL-12 resulted in complete regression or substantial inhibition of 38C13 B-cell lymphoma, whereas pIL-12 delivered by gene gun or intramuscular injection without EP showed little therapeutic effect. Impressive antitumor activity by intramuscular EP was also demonstrated in animals with advanced malignant disease. At day 14 after 38C13 tumor inoculation, all animals were found to carry large tumors and to have metastases; without treatment, most died within a week. A single intramuscular EP of pIL-12 resulted in regression of 50% of large subcutaneous tumors and significantly prolonged the lifespan of these animals. Moreover, animals that were previously cured of 38C13 tumors by in vivo EP treatment significantly suppressed tumor growth when challenged 60 days later. In vivo EP of the IL-12 gene was also effective in suppressing subcutaneous and lung metastatic tumors of CT-26 colon adenocarcinoma and B16F1 melanoma cells. Together, these results show that intramuscular electrotransfer of the IL-12 gene may represent a simple and effective strategy for cancer treatment.
Lee
Shan-Chih
SC
National Health Research Institutes, Taipei, Taiwan, ROC.
Wu
Chang-Jer
CJ
Wu
Pin-Yi
PY
Huang
Yi-Ling
YL
Wu
Cheng-Wen
CW
Tao
Mi-Hua
MH
D000818:Animals; D004305:Dose-Response Relationship, Drug; D018274:Electroporation; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal; D009362:Neoplasm Metastasis / Q000517:prevention & control* / Q000628:therapy; D009374:Neoplasms, Experimental / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D018664:Interleukin-12