Composition for treating tumors that produce disialoganglioside GD2, comprises human antibody fragment able to induce anti-idiotypic antibodies

摘要

Studies using monoclonal antibodies against the disialoganglioside GD2 in tumours of neuroectodermal origin, such as neuroblastoma, melanoma and small-cell lung carcinoma have shown that immunisation against tumour-associated antigens is probably necessary to obtain therapeutic long-term effects. Direct vaccination with GD2 is therapeutically unsuitable owing to difficulties of purification, poor water solubility and low immunogenity. Antiidiotypic antibodies (anti-Ids) could be used as a replacement against anti-GD2 antibodies, said antiidiotypic antibodies imitating GD2 in such a way that they act immunogenically against GD2. The anti-Ids against GD2 antibodies used in previous studies are only sub-optimally suitable for the therapy as a result of their murine origin. Human anti-Ids, currently produced using the EBV-hybridoma technique have not been used in commercial, therapeutic applications notably because of their instability. The aim of the invention is therefore to clone stable anti-Ids of human origin against GD2 antibodies, using recombinant techniques (phage display). Said anti-Ids can be used as medicaments for the treatment of (GD2) positive tumours and in the associated diagnostics. The presence of recombinant Fab with a known sequence allows the optimal preparation of the vaccines as a fusion protein or DNA vaccines.