Adjuvant vaccination with melanoma antigen-pulsed dendritic cells in stage III melanoma patients.
Dendritic cells may be successfully used to induce in vivo-specific anti-tumor responses when combined with the appropriate antigen in the appropriate context. The purpose of this study was to evaluate efficacy of peptide-loaded DC vaccine in high-risk stage III melanoma patients after lymph node dissection (LND). HLA-A2+, -A1+, or -A3+ melanoma patients (N=22), stage III, N1b-N3, received 5–16 (median: 11) DC vaccines loaded with MHC class-I-restricted melanoma peptides respective to the patient’s haplotype, and with autologous tumor lysate, if available. Vaccinated patients were matched to unvaccinated stage III controls (22 of 869) by sex, number of metastatic lymph nodes, extracapsular involvement, LND type, Breslow stage, and ulceration. Vaccination elicited cutaneous delayed-type hypersensitivity (DTH) or/and IFN-γ-producing CD8+ cell response to melanoma peptides in 15 of 22 patients. Three-year overall survival (OS) rate was 68.2% in the vaccinated group versus 25.7% in the control group, P value accounting for matching: 0.0290. In a Cox regression model, hazard ratio (HR) for death of vaccinated patients was 0.31 [95% confidence interval (CI): 0.10–0.94]. The corresponding values for 3-year disease-free survival rate were 40.9 versus 14.5%, P=0.1083; HR of recurrence for vaccinated, 0.46 (95% CI: 0.18–1.22). There was no grade>1 toxicity. The DC/peptide vaccine was well tolerated and elicited immune responses to melanoma antigens. Vaccinated patients had significantly longer OS after LND than the matched controls, but a significant improvement in the primary endpoint DFS was not achieved.
Department of Immunology, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, ul. Roentgena 5, 02-781 Warszawa, Poland. sergiusz@coi.waw.pl
Sergiusz
S
Markowicz
Zbigniew I
ZI
Nowecki
Piotr
P
Rutkowski
Andrzej W
AW
Lipkowski
Marzena
M
Biernacka
Anna
A
Jakubowska-Mucka
Tomasz
T
Switaj
Aleksandra
A
Misicka
Henryk
H
Skurzak
Hanna
H
Polowniak-Pracka
Jan
J
Walewski
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D014611:Vaccination / Q000009:adverse effects
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006680:HLA Antigens; D016178:Granulocyte-Macrophage Colony-Stimulating Factor