Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients.
OBJECTIVE
We evaluated the feasibility, safety, and immunogenicity of mature, peptide-pulsed dendritic cell (DC) vaccines administered by different routes.


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.


CONCLUSIONS
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.
Bedrosian
Isabelle
I
Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mick
Rosemarie
R
Xu
Shuwen
S
Nisenbaum
Harvey
H
Faries
Mark
M
Zhang
Paul
P
Cohen
Peter A
PA
Koski
Gary
G
Czerniecki
Brian J
BJ
D000279:Administration, Cutaneous; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000633:toxicity; D003713:Dendritic Cells / Q000276:immunology*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D016219:Immunotherapy, Adoptive; D007275:Injections, Intravenous; D008198:Lymph Nodes; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017063:Outcome Assessment, Health Care; D014611:Vaccination
D019496:Cancer Vaccines