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J Clin Oncol. 2003 Oct 15;21(20):3826-35.

Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients.

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1
Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

PURPOSE:

We evaluated the feasibility, safety, and immunogenicity of mature, peptide-pulsed dendritic cell (DC) vaccines administered by different routes.

PATIENTS AND METHODS:

We performed a randomized, phase I, dose-escalation study in 27 patients with metastatic melanoma receiving four autologous peptide-pulsed DC vaccinations. Patients were randomly assigned to an intravenous (IV), intranodal (IN), or intradermal (ID) route of administration (ROA). For each route, primary end points were dose-limiting toxicity, maximum-tolerated dose, and T-cell sensitization. Sensitization was evaluated through tetramer staining, in vitro peptide recognition assays, and delayed-type hypersensitivity (DTH) responses.

RESULTS:

Twenty-two (81.5%) of 27 patients completed all four vaccinations. Vaccinations were well tolerated; a few patients exhibited grade 1 to 2 toxicities including rash, fever, and injection site reaction. All routes of administration induced comparable increases in tetramer-staining CD8+ T cells (five of seven IV, four of seven IN, and four of six ID patients). However, the IN route induced significantly higher rates for de novo development of CD8+ T cells that respond by cytokine secretion to peptide-pulsed targets (six [85.7%] of seven IN patients v two [33%] of six ID patients v none [0%] of six IV patients; P =.005) and de novo DTH (seven [87.5%] of eight IN patients v two [33.3%] of six ID patients v one [14.3%] of seven IV patients; P =.01) compared with other routes.

CONCLUSION:

Administration of this peptide-pulsed mature DC vaccine by IN, IV, or ID routes is feasible and safe. IN administration seems to result in superior T-cell sensitization as measured by de novo target-cell recognition and DTH priming, indicating that IN may be the preferred ROA for mature DC vaccines.

PMID:
14551301
DOI:
10.1200/JCO.2003.04.042
[Indexed for MEDLINE]
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