Recombinant antibodies in the immunotherapy of neuroblastoma: perspectives of new developments

The impact of monoclonal antibodies (mAbs) in the treatment of human tumors has greatly increased in recent years. mAb engineering has allowed reducing the immunogenicity of therapeutic antibodies as well as improving their biodistribution. Furthermore, engineered mAbs have been used to vehiculate toxins, drugs and other anti-neoplastic agents to the tumor site. In the case of neuroblastoma (NB), a pediatric malignancy originating from the neural crest, both murine and chimeric antibodies against the tumor associated antigen GD2 have been tested in clinical trials, either alone or in combination with cytokines. A novel promising approach to mAb engineering is the small immuno-protein (SIP) technique, whereby the variable regions of heavy and light chains of a mAb with a given specificity are connected to the dimerizing CH3 domain of an immunoglobulin molecule. The current status of mAb therapy for NB is discussed together with our preliminary results on the generation of novel anti-GD2 molecules using the SIP technique.