Immunological long-term follow-up of neuroblastoma stage IV patients after anti-GD2 CH14.18 antibody treatment.

Abstract

3029 Background: Neuroblastoma stage IV is associated with low cure rates. Treatment with the GD2 antibody ch14.18 could improve the long-term overall survival. Apart from GD2 other tumor antigens (TA) are expressed in neuroblastoma and studies implicated that T-cell responses to TA are associated with a better outcome. For the present study we analyzed the immune response in long term neuroblastoma survivors treated with anti GD2 ch14.18. Methods: Blood and serum of 17 neuroblastoma long-term survivors after GD2 therapy with > 5 years follow up (patients group) and 17 age and gender matched healthy donors (control group) were analyzed. Serum was analyzed for antibodies binding to neuroblastoma cell lines and antibodies to a nominal antigen GD2. T cells were stimulated with overlapping peptides of the tumor antigens (TA) NY-ESO-1, WT-1, Survivin, MAGE-A1 and two mimotope peptides to GD2 for 10 days and analyzed for IFN-γ secretion in flow cytometry. Results: T-cell responses to at least one TA could be found in 82% of healthy and in 93% of patients with no significant difference in the number of TA responders between the two groups to any of these TA (Fisher´s exact test). In contrast, T-cell responses to at least one of the GD2 mimotopes were found in 53% of neuroblastoma survivors but in 0% of healthy donors. Moreover, even priming with GD2 mimotope loaded dendritic cells did not induce a T-cell response in healthy donor cells. No differences between patient and control group could be detected in binding of antibodies to neuroblastoma cell lines and no GD2-specific antibodies were detected in patients and controls. Conclusions: Survivors of neuroblastoma treated with anti-GD2 ch14.18 demonstrated robust T-cell responses to neuroblastoma associated TA that was comparable to healthy donors. This could enable patients to attack minimal residual disease efficiently. Moreover more than half of the patients had T-cell responses to GD2 which could be an effect of the GD2 antibody therapy. Our results show that involvement of the cellular immune system might have an impact on the better outcome of this treatment in stage IV neuroblastoma patients.