고위험군 신경모세포종에서 Anti-GD2 Monoclonal Antibody (Dinutuximab)와 GM-CSF, Interleukin 2, Cis-retinoic Acid의 병합요법

Abstract

Neuroblastoma, one of the most common solid tumors in early childhood, exhibits aberrant cell-surface glycosylation patterns. In neuroblastoma, disialoganglioside (GD2) is expressed homogeneously and abundantly on 100% of neuroblastoma cells. GD2 is a good tumor marker for developing an anti-tumor-monoclonal antibody (mAb) to neuroblastoma. Immunotherapy, using anti-GD2-mAb, has been tried since last 20 years to improve the prognosis of high risk neuroblastoma patients who show a 5-year survival rate of less than 30% regardless of an intense multimodal therapy. Since the first clinical trial of murine anti-GD2-mAb 3F8 had been performed, multiple clinical studies showed that anti-GD2-mAb might improve the prognosis of high risk neuroblastoma patients. Anti-GD2-mAb removes the neuroblastoma cells via apoptosis by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity. To elicit a stronger ADCC response to antibody therapy, cytokines such as, GM-CSF and interleukin-2 are concomitantly administered, which stimulate the natural anti-tumor activity of the immune system. Children’s Oncology Group performed a study of chimeric anti-GD2-mAb (ch14.18) administration with GM-CSF, IL-2 for high risk neuroblastoma patients and showed the improvement of overall survival rate. Based on this study US FDA approved the chimeric anti-GD2-mAb (commercially manufactured dinutuximab) for the treatment of high risk neuroblastoma. Dinutuximab is the the first mAb for use in combination of cytokines for the maintenance treatment of pediatric patients with high risk neuroblastoma who achieve at least a partial response to intensified multimodal therapy. The first anti-tumor-mAb used for children, dinutuximab, could be the base of further development of mAb against the cancers in childhood.