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Fest, Stefan; Huebener, Nicole; Weixler, Silke; Bleeke, Matthias; Zeng, Yan; Strandsby, Anne; Volkmer-Engert, Rudolf; Landgraf, Christiane; Gaedicke, Gerhard; Riemer, Angelika B.; Michalsky, Elke; Jaeger, Ines S.; Preissner, Robert; Förster-Wald, Elisabeth; Jensen-Jarolim, Erika; Lode, Holger N.

Characterization of GD2 Peptide Mimotope DNA Vaccines Effective against Spontaneous Neuroblastoma Metastases

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  • Media type: E-Article
  • Title: Characterization of GD2 Peptide Mimotope DNA Vaccines Effective against Spontaneous Neuroblastoma Metastases
  • Contributor: Fest, Stefan; Huebener, Nicole; Weixler, Silke; Bleeke, Matthias; Zeng, Yan; Strandsby, Anne; Volkmer-Engert, Rudolf; Landgraf, Christiane; Gaedicke, Gerhard; Riemer, Angelika B.; Michalsky, Elke; Jaeger, Ines S.; Preissner, Robert; Förster-Wald, Elisabeth; Jensen-Jarolim, Erika; Lode, Holger N.
  • imprint: American Association for Cancer Research (AACR), 2006
  • Published in: Cancer Research
  • Language: English
  • DOI: 10.1158/0008-5472.can-06-1158
  • ISSN: 0008-5472; 1538-7445
  • Keywords: Cancer Research ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:p>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 (Kd = 12.3 × 10−5 mol/L for MA and 5.3 × 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. (Cancer Res 2006; 66(21): 10567-75)</jats:p>
  • Access State: Open Access