Dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma

Expert Rev Clin Pharmacol. 2016;9(5):647-53. doi: 10.1586/17512433.2016.1160775. Epub 2016 Mar 21.

Abstract

Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood, with 60% of patients presenting with high risk (HR) NB by means of clinical, pathological and biological features. The 5-year survival rate for HR-NB remains below 40%, with the majority of patients suffering relapse from chemorefractory tumor. Immunotherapy is the main strategy against minimal residual disease and clinical experience has mostly focused on monoclonal antibodies (MoAb) against the glycolipid disialoganglioside GD2. Three anti-GD2 antibodies have been tested in the clinic including murine 14G2a, human-mouse chimeric ch14.18 and 3F8. Anti-GD2 MoAb induces cellular cytoxicity against NB and is most effective when effector cells like natural killer cells, granulocytes and macrophages are amplified by cytokines. The combination of cytokines IL-2 and GM-CSF with the anti-GD2 MoAb ch14.18 (Dinutuximab) has shown a significant improvement in outcome for HR-NB. The FDA and EMA approved dinutuximab (Unituxin(R)) in 2015 for the treatment of patients with HR-NB who achieved at least a partial response after multimodality therapy.

Keywords: GM-CSF; Interleukin 2; Neuroblastoma; Unituxin; anti-GD2 immunotherapy; children’s cancer; chimeric antibodies; dinutuximab; orphan drugs.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Child
  • Drug Resistance, Neoplasm
  • Humans
  • Immunotherapy
  • Neuroblastoma / drug therapy*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • dinutuximab