Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients

Eur J Immunol. 2012 Nov;42(11):3049-61. doi: 10.1002/eji.201142361. Epub 2012 Aug 28.


Optimal vaccine strategies must be identified for improving T-cell vaccination against infectious and malignant diseases. MelQbG10 is a virus-like nano-particle loaded with A-type CpG-oligonucleotides (CpG-ODN) and coupled to peptide(16-35) derived from Melan-A/MART-1. In this phase IIa clinical study, four groups of stage III-IV melanoma patients were vaccinated with MelQbG10, given (i) with IFA (Montanide) s.c.; (ii) with IFA s.c. and topical Imiquimod; (iii) i.d. with topical Imiquimod; or (iv) as intralymph node injection. In total, 16/21 (76%) patients generated ex vivo detectable Melan-A/MART-1-specific T-cell responses. T-cell frequencies were significantly higher when IFA was used as adjuvant, resulting in detectable T-cell responses in all (11/11) patients, with predominant generation of effector-memory-phenotype cells. In turn, Imiquimod induced higher proportions of central-memory-phenotype cells and increased percentages of CD127(+) (IL-7R) T cells. Direct injection of MelQbG10 into lymph nodes resulted in lower T-cell frequencies, associated with lower proportions of memory and effector-phenotype T cells. Swelling of vaccine site draining lymph nodes, and increased glucose uptake at PET/CT was observed in 13/15 (87%) of evaluable patients, reflecting vaccine triggered immune reactions in lymph nodes. We conclude that the simultaneous use of both Imiquimod and CpG-ODN induced combined memory and effector CD8(+) T-cell responses.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Aminoquinolines / administration & dosage
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Flow Cytometry
  • Freund's Adjuvant / administration & dosage
  • Humans
  • Imiquimod
  • Immunologic Memory / immunology*
  • Ligands
  • Lipids / administration & dosage
  • MART-1 Antigen / immunology
  • Melanoma / immunology*
  • Melanoma / therapy*
  • Nanoparticles / administration & dosage*
  • Oligodeoxyribonucleotides / immunology
  • Skin Neoplasms / immunology*
  • Statistics, Nonparametric
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 9 / immunology


  • Adjuvants, Immunologic
  • Aminoquinolines
  • CPG-oligonucleotide
  • Cancer Vaccines
  • Ligands
  • Lipids
  • MART-1 Antigen
  • Oligodeoxyribonucleotides
  • TLR7 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • incomplete Freund's adjuvant
  • Freund's Adjuvant
  • Imiquimod