title: Evaluation of toxicity following electrically mediated interleukin-12 gene delivery in a B16 mouse melanoma model.
abstract: OBJECTIVE
  Interleukin-12 (IL-12) has potential as an immunotherapeutic agent for the treatment of cancer but is unfortunately associated with toxicity. Delivery of a plasmid encoding IL-12 with electroporation induces an antitumor effect in the B16 mouse melanoma model without serious side effects. To translate this observation to the clinic, an evaluation of toxicity was done in the mouse model.
  
  
  METHODS
  Weight change, tumor response, blood chemistry and hematology values, and serum IL-12 levels were evaluated. Multiple tissues were analyzed histopathologically.
  
  
  RESULTS
  A pronounced reduction in tumor volume, including a large percentage of complete regressions, was observed after electrically mediated gene therapy. No significant increases in serum IL-12 levels were detected. Tumor-bearing mice showed an increased number of atypical hematology values when compared with normal naive controls. Statistically significant differences in chemistry and hematology values were observed sporadically in most of the standard chemistry and hematology categories in all groups. The only histopathologic abnormality specific to the animals receiving both plasmid and electroporation was inflammation associated with the kidney at the last time point.
  
  
  CONCLUSIONS
  In general, mice that received both plasmid and electroporation showed the least abnormal histopathologic findings and were found to be in the best health, reflecting the reduced burden of disease. No significant toxic effects due to the IL-12 gene therapy were observed.
authors.affiliation: Department of Medical Microbiology and Immunology, University of South Florida, Tampa 33612, USA.
authors.forename: Loree
authors.initials: L
authors.lastname: Heller
authors.forename: Kathleen
authors.initials: K
authors.lastname: Merkler
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Westover
authors.forename: Yolmari
authors.initials: Y
authors.lastname: Cruz
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.forename: Kaaron
authors.initials: K
authors.lastname: Benson
authors.forename: Adil
authors.initials: A
authors.lastname: Daud
authors.forename: Richard
authors.initials: R
authors.lastname: Heller
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018274:Electroporation; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D007668:Kidney / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D010957:Plasmids; D012878:Skin Neoplasms / Q000628:therapy*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D018664:Interleukin-12