Characterization of GD2 peptide mimotope DNA vaccines effective against spontaneous neuroblastoma metastases

Cancer Res. 2006 Nov 1;66(21):10567-75. doi: 10.1158/0008-5472.CAN-06-1158.


Disialoganglioside GD2 is an established target for immunotherapy in neuroblastoma. We tested the hypothesis that active immunization against the glycolipid GD2 using DNA vaccines encoding for cyclic GD2-mimicking decapeptides (i.e., GD2 mimotopes) is effective against neuroblastoma. For this purpose, two GD2 peptide mimotopes (MA and MD) were selected based on docking experiments to anti-GD2 antibody ch14.18 (binding free energy: -41.23 kJ/mol for MA and -48.06 kJ/mol for MD) and Biacore analysis (K(d) = 12.3 x 10(-5) mol/L for MA and 5.3 x 10(-5) mol/L for MD), showing a higher affinity of MD over MA. These sequences were selected for DNA vaccine design based on pSecTag2-A (pSA) also including a T-cell helper epitope. GD2 mimicry was shown following transfection of CHO-1 cells with pSA-MA and pSA-MD DNA vaccines, with twice-higher signal intensity for cells expressing MD over MA. Finally, these DNA vaccines were tested for induction of tumor protective immunity in a syngeneic neuroblastoma model following oral DNA vaccine delivery with attenuated Salmonella typhimurium (SL 7207). Only mice receiving the DNA vaccines revealed a reduction of spontaneous liver metastases. The highest anti-GD2 humoral immune response and natural killer cell activation was observed in mice immunized with the pSA-MD, a finding consistent with superior calculated binding free energy, dissociation constant, and GD2 mimicry potential for GD2 mimotope MD over MA. In summary, we show that DNA immunization with pSA-MD may provide a useful strategy for active immunization against neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Cricetinae
  • Gangliosides / genetics
  • Gangliosides / immunology*
  • Interferon-gamma / biosynthesis
  • Mice
  • Neoplasm Metastasis / prevention & control
  • Neuroblastoma / immunology
  • Neuroblastoma / prevention & control
  • Neuroblastoma / secondary*
  • Vaccination
  • Vaccines, DNA / immunology*


  • Cancer Vaccines
  • Gangliosides
  • Vaccines, DNA
  • ganglioside, GD2
  • Interferon-gamma