Targeting the disialoganglioside GD2 in neuroblastoma using a phage display derived oligopeptide

Introduction: High expression of GD2 on neuroblastoma cells renders this disialoganglioside an attractive target for novel therapeutic and diagnostic approaches. Anti-GD2 antibodies have already entered the clinical stage, but GD2-based markers could also serve in diagnostics and for imaging purposes.

Method: We performed a combined in vivo and in vitro phage display screen to identify GD2-specific peptides. The resulting phages were tested for their binding specificity and their ability to home to a xenograft neuroblastoma tumor. Phage-derived peptides were further characterizsed using MTT-Assays and radioactively labeled with either In111 or Ga68 to analyse their tumor homing capacity using in vivo imaging

Results: Phages specifically binding to GD2 were identified in vitro and their in vivo accumulation in xenografted tumors was confirmed. Peptides derived from the phages were shown to competitively inhibit the phage binding to GD2 in vitro and in vivo. GD2-binding peptides were shown to reduce cell viability of neuroblastoma cells in vitro when compared to control peptides. Finally, Ga68- labeled GD2-binding oligopeptides accumulated in tumor tissue as deduced from combined PET/MR imaging.

Conclusion: We demonstrate that peptide ligands to the disialoganglioside GD2 generated via a phage display screen can home to neuroblastoma tumor-tissue. Therefore this peptide may be a new useful tool for diagnostic and therapeutic procedures in neuroblastoma and other tumors expressing GD2.