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

Academic Article
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Overview

authors

  • Zeng, Y.
  • Jiang, J.
  • Huebener, N.
  • Wenkel, J.
  • Gaedicke, G.
  • Xiang, Rong
  • Lode, H. N.

publication date

  • October 2005

journal

  • Cancer Letters  Journal

abstract

  • 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.

subject areas

  • Animals
  • Base Sequence
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • DNA Primers
  • Gene Transfer Techniques
  • Genetic Therapy
  • Humans
  • Interleukin-2
  • Liver Neoplasms
  • Membrane Proteins
  • Mice
  • Neuroblastoma
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Research

keywords

  • Ch14.18-IL-2
  • GD2
  • fractalkine
  • gene therapy
  • immunotherapy
  • neuroblastoma
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Identity

International Standard Serial Number (ISSN)

  • 0304-3835

Digital Object Identifier (DOI)

  • 10.1016/j.canlet.2005.01.057

PubMed ID

  • 15953676
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Additional Document Info

start page

  • 187

end page

  • 193

volume

  • 228

issue

  • 1-2

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