Medical Oncology

, Volume 29, Issue 4, pp 2966–2977

Adjuvant vaccination with melanoma antigen-pulsed dendritic cells in stage III melanoma patients

  • Sergiusz Markowicz
  • Zbigniew I. Nowecki
  • Piotr Rutkowski
  • Andrzej W. Lipkowski
  • Marzena Biernacka
  • Anna Jakubowska-Mucka
  • Tomasz Switaj
  • Aleksandra Misicka
  • Henryk Skurzak
  • Hanna Polowniak-Pracka
  • Jan Walewski
Original Paper

DOI: 10.1007/s12032-012-0168-1

Cite this article as:
Markowicz, S., Nowecki, Z.I., Rutkowski, P. et al. Med Oncol (2012) 29: 2966. doi:10.1007/s12032-012-0168-1

Abstract

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.

Keywords

Adjuvant vaccination Cancer vaccine Dendritic cells Melanoma Melanoma peptide 

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Sergiusz Markowicz
    • 1
  • Zbigniew I. Nowecki
    • 2
  • Piotr Rutkowski
    • 2
  • Andrzej W. Lipkowski
    • 3
  • Marzena Biernacka
    • 1
  • Anna Jakubowska-Mucka
    • 1
  • Tomasz Switaj
    • 2
  • Aleksandra Misicka
    • 3
  • Henryk Skurzak
    • 1
  • Hanna Polowniak-Pracka
    • 4
  • Jan Walewski
    • 5
  1. 1.Department of ImmunologyMaria Sklodowska-Curie Memorial Institute and Oncology CentreWarszawaPoland
  2. 2.Department of Soft Tissue/Bone Sarcoma and MelanomaMaria Sklodowska-Curie Memorial Institute and Oncology CentreWarszawaPoland
  3. 3.Neuropeptide Department, Mossakowski Medical Research CentrePolish Academy of SciencesWarszawaPoland
  4. 4.Department of MicrobiologyMaria Sklodowska-Curie Memorial Institute and Oncology CentreWarszawaPoland
  5. 5.Department of Lymphoid MalignanciesMaria Sklodowska-Curie Memorial Institute and Oncology CentreWarszawaPoland

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