title: Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma.
abstract: OBJECTIVE
  Gene-based immunotherapy for cancer is limited by the lack of safe, efficient, reproducible, and titratable delivery methods. Direct injection of DNA into tissue, although safer than viral vectors, suffers from low gene transfer efficiency. In vivo electroporation, in preclinical models, significantly enhances gene transfer efficiency while retaining the safety advantages of plasmid DNA.
  
  
  METHODS
  A phase I dose escalation trial of plasmid interleukin (IL)-12 electroporation was carried out in patients with metastatic melanoma. Patients received electroporation on days 1, 5, and 8 during a single 39-day cycle, into metastatic melanoma lesions with six 100-mus pulses at a 1,300-V/cm electric field through a penetrating six-electrode array immediately after DNA injection. Pre- and post-treatment biopsies were obtained at defined time points for detailed histologic evaluation and determination of IL-12 protein levels.
  
  
  RESULTS
  Twenty-four patients were treated at seven dose levels, with minimal systemic toxicity. Transient pain after electroporation was the major adverse effect. Post-treatment biopsies showed plasmid dose proportional increases in IL-12 protein levels as well as marked tumor necrosis and lymphocytic infiltrate. Two (10%) of 19 patients with nonelectroporated distant lesions and no other systemic therapy showed complete regression of all metastases, whereas eight additional patients (42%) showed disease stabilization or partial response.
  
  
  CONCLUSIONS
  This report describes the first human trial, to our knowledge, of gene transfer utilizing in vivo DNA electroporation. The results indicated this modality to be safe, effective, reproducible, and titratable.
authors.affiliation: Cutaneous Oncology and Experimental Therapeutics Programs, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL, USA. adaud@medicine.ucsf.edu
authors.forename: Adil I
authors.initials: AI
authors.lastname: Daud
authors.forename: Ronald C
authors.initials: RC
authors.lastname: DeConti
authors.forename: Stephanie
authors.initials: S
authors.lastname: Andrews
authors.forename: Patricia
authors.initials: P
authors.lastname: Urbas
authors.forename: Adam I
authors.initials: AI
authors.lastname: Riker
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
authors.forename: Pamela N
authors.initials: PN
authors.lastname: Munster
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sullivan
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Ugen
authors.forename: Jane L
authors.initials: JL
authors.lastname: Messina
authors.forename: Richard
authors.initials: R
authors.lastname: Heller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018274:Electroporation / Q000379:methods*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D018664:Interleukin-12 / Q000032:analysis / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010957:Plasmids / Q000008:administration & dosage* / Q000009:adverse effects; D012878:Skin Neoplasms / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D018664:Interleukin-12