HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

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.
AuthorsYan Zeng, Jikai Jiang, Nicole Huebener, Jens Wenkel, Gerhard Gaedicke, Rong Xiang, Holger N Lode
JournalCancer letters (Cancer Lett) Vol. 228 Issue 1-2 Pg. 187-93 (Oct 18 2005) ISSN: 0304-3835 [Print] Ireland
PMID15953676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Cx3cl1 protein, mouse
  • DNA Primers
  • Interleukin-2
  • Membrane Proteins
Topics
  • 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, therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: