Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with Stage IV melanoma.
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.
Tagawa
Scott T
ST
Department of Medicine, Keck-University of Southern California School of Medicine, Los Angeles, California, USA.
Lee
Peter
P
Snively
Jolie
J
Boswell
William
W
Ounpraseuth
Song
S
Lee
Sandra
S
Hickingbottom
Barbara
B
Smith
John
J
Johnson
Denise
D
Weber
Jeffrey S
JS
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*
D019496:Cancer Vaccines; D019444:Vaccines, DNA