title: Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with Stage IV melanoma.
abstract: BACKGROUND
  Based on the likelihood of transfecting large numbers of local antigen-presenting cells, a Phase I study in patients with Stage IV melanoma was conducted to determine the practicality, toxicity of, and immune responses to repeated infusions into a groin lymph node of escalating doses of a DNA plasmid encoding tyrosinase epitopes.
  
  
  METHODS
  Cohorts of 8 patients each received 200 microg, 400 microg, or 800 microg of DNA intranodally by pump over 96 hours every 14 days for 4 cycles. Blood was collected for immunologic assays and to measure plasmid in serum prior to treatment, 4 weeks later, and 8 weeks later. Scans and X-rays were performed at baseline and after 8 weeks.
  
  
  RESULTS
  Treatment was tolerated well, with only five patients demonstrating Grade 1-2 toxicity. Vaccine delivery by 96-hour infusions of plasmid into a groin lymph node resulted in only 1 episode of catheter leakage in 107 cannulations. Detection of plasmid in serum was rare and transient in two patients. Immune responses by peptide-tetramer assay to tyrosinase 207-216 were detected in 11 of 26 patients. No clinical responses were seen. Survival of the heavily pretreated patients on this trial was unexpectedly long, with 16 of 26 patients alive at a median follow-up of 12 months.
  
  
  CONCLUSIONS
  Infusion of a DNA plasmid vaccine into a groin lymph node was practical and well tolerated. Immune responses to a novel tyrosinase epitope were noted. Overall survival in this trial of heavily pretreated patients was unexpectedly long, with 16 of 26 patients alive after a follow-up of 12 months, favoring immune responders.
authors.affiliation: Department of Medicine, Keck-University of Southern California School of Medicine, Los Angeles, California, USA.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.forename: Peter
authors.initials: P
authors.lastname: Lee
authors.forename: Jolie
authors.initials: J
authors.lastname: Snively
authors.forename: William
authors.initials: W
authors.lastname: Boswell
authors.forename: Song
authors.initials: S
authors.lastname: Ounpraseuth
authors.forename: Sandra
authors.initials: S
authors.lastname: Lee
authors.forename: Barbara
authors.initials: B
authors.lastname: Hickingbottom
authors.forename: John
authors.initials: J
authors.lastname: Smith
authors.forename: Denise
authors.initials: D
authors.lastname: Johnson
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D010957:Plasmids; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D019444:Vaccines, DNA