Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with Stage IV melanoma.

Cancer 2003 Jul;98(1):144-54

Department of Medicine, Keck-University of Southern California School of Medicine, Los Angeles, California, USA.

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.

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http://dx.doi.org/10.1002/cncr.11462DOI Listing
July 2003
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References

(Supplied by CrossRef)

Hsueh et al.
J Clin Oncol. 1998

Rosenberg et al.
Nat Med. 1998

Helling et al.
Cancer Res. 1995

Sondak et al.
J Clin Oncol. 2002

Sosman et al.
J Clin Oncol. 2002

Wolff et al.
Science. 1999

Ulmer et al.
Science. 1993

Ulmer et al.
Vaccine. 1997

Raz et al.
Proc Natl Acad Sci USA. 1994

Donnelly et al.
Annu Rev Immunol. 1997

Mincheff et al.
Eur Urol. 2000

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