Fractalkine gene therapy for neuroblastoma is more effective in combination with targeted IL-2

Cancer Lett. 2005 Oct 18;228(1-2):187-93. doi: 10.1016/j.canlet.2005.01.057.


The induction of tumor protective immunity against neuroblastoma remains a major challenge for active immunotherapy. Fractalkine is a unique Th1 CX3C chemokine known to induce adhesion and migration of leukocytes mediated by both, a membrane-bound and soluble form, respectively. Here, we tested the hypothesis that chemokine gene therapy with fractalkine (FKN) induces an effective anti-neuroblastoma immune response amplified by targeted IL-2 using the anti-GD2 antibody ch14.18 fused with IL-2 (ch14.18-IL-2). For this purpose, NXS2 cells were genetically engineered to stably produce murine FKN (NXS2-FKN). Transcription and expression of the mFKN gene in tumor tissue of mice inoculated with NXS2-FKN cells were demonstrated in vivo. Importantly, mFKN exhibited a reduction in primary tumor growth and spontaneous liver metastases in syngenic A/J mice. This effect was boosted by targeted IL-2 using small non-curative doses of ch14-18-IL-2. The amplification of the FKN induced immune response was specific, since a non-specific antibody-IL-2 fusion protein ch225-IL-2 was ineffective. In summary, we demonstrated for the first time that chemokine gene therapy is amplified by targeted IL-2 suggesting a combination of both strategies as an adjuvant therapy for neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Base Sequence
  • Chemokine CX3CL1
  • Chemokines, CX3C / genetics*
  • DNA Primers
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Humans
  • Interleukin-2 / therapeutic use*
  • Liver Neoplasms / secondary
  • Membrane Proteins / genetics*
  • Mice
  • Neuroblastoma / drug therapy
  • Neuroblastoma / therapy*


  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Cx3cl1 protein, mouse
  • DNA Primers
  • Interleukin-2
  • Membrane Proteins