Generation of Peptide mimics of Melanoma Antigen GD2

Disialoganglioside GD2, a relevant tumor antigen, is overexpressed on numerous malignancies as melanomas, leptomeningeal cancers, osteosarcomas and neuroblastomas. The chimeric anti-GD2 antibody ch14.18 is presently applied in clinical trials for targeting GD2 overexpressing advanced melanoma and osteosarcoma, as well as neuroblastoma. For developing an active immunotherapy, we defined peptide mimics of the 14.18 epitope on GD2. By biopanning a random peptide phage display library with the antibody, thirteen GD2 mimotope candidates could be identified. They were proven to be true epitope mimics by mimicry tests in the ELISA format. Using three-dimensional computer modeling (BALLView), we were able to demonstrate that two selected mimotopes fitted into the antigen binding pouch of a GD2 specific antibody in the same manner as original antigen GD2. We conclude that we succeeded in generating peptide mimics of the carbohydrate antigen GD2. In contrast to GD2 which is a poor immunogen, these peptides might be utilized to develop an active immunization against overexpressing GD2 tumors.