Neuroblastoma (NB) is a challenging
malignancy of the sympathetic nervous tissue characterized by a very poor prognosis. One important marker for NB is the expression of
tyrosine hydroxylase (TH), the first-step
enzyme of
catecholamine biosynthesis. We could show stable and high TH gene expression in 67 NB samples independent of the clinical stage. Based on this observation, we addressed the question of whether xenogeneic TH
DNA vaccination is effective in inducing an anti-NB immune response. For this purpose, we generated three
DNA vaccines based on pCMV-F3Ub and pBUD-CE4.1 plasmids encoding for human (h)THcDNA (A), hTH minigene (B), and hTHcDNA in combination with the proinflammatory
cytokine interleukin 12 (C), and tested prophylactic and therapeutic efficacy to suppress primary
tumor growth and spontaneous
metastasis. Here we report that xenogeneic TH
DNA vaccination was effective in eradicating established primary
tumors and inhibiting
metastasis. Interestingly, this effect could not be enhanced by adding the Th1
cytokine interleukin 12. However, increased IFN-gamma production and NB cytotoxicity of effector cells harvested from vaccinated mice suggested the participation of
tumor-specific CTLs in the immune response. The depletion of CD8(+)T cells completely abrogated the hTH
vaccine-mediated anti-NB immune response. Furthermore, rechallenging of surviving mice resulted in reduced primary
tumor growth, indicating the induction of a memory immune response. In conclusion, xenogeneic immunization with TH-derived
DNA vaccines is effective against NB, and may open a new venue for a novel and effective immunotherapeutic strategy against this challenging childhood
tumor.