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.