title: Targeted immunotherapy for high-risk neuroblastoma--the role of monoclonal antibodies.
abstract: OBJECTIVE
  To systematically review clinical trials evaluating anti-disialoganglioside (GD2) antibodies in treating high-risk neuroblastoma in children.
  
  
  METHODS
  A literature search was conducted in PubMed/MEDLINE, International Pharmaceutical Abstracts, and Cumulative Index of Nursing and Allied Health Literature (all searches 1990-August 2012) using the terms neuroblastoma, immunotherapy, 3F8, ch14.18, and hu14.18. Meeting abstracts presented between 1990 and 2012 from the American Society of Clinical Oncology, European Society for Medical Oncology, the American Society of Pediatric Hematology Oncology, Society of Surgical Oncology, and the American Society of Hematology were also evaluated.
  
  
  METHODS
  All completed and ongoing clinical trials of anti-GD2 antibodies in neuroblastoma were included. References from selected articles were also reviewed to identify additional citations.
  
  
  RESULTS
  In 1999, the results of a Children's Cancer Group trial established that consolidation therapy after induction, surgery, and radiation should include purged autologous stem cell rescue followed by maintenance with isotretinoin. Overall survival at 7 years with this regimen remains below 30%. Over the following decade, antibodies targeting GD2, a surface antigen found on the surface of neuroblastoma cells, have emerged as a major therapeutic development for high-risk neuroblastoma. Anti-GD2 antibodies incite immune-mediated cytotoxicity toward neuroblastoma cells when given as monotherapy or in combination with cytokines such as sargramostim (granulocyte-macrophage colony-stimulating factor) or aldesleukin (interleukin-2). Responses to anti-GD2 agents appear most notable in patients with minimal residual disease following standard therapy. A chimeric preparation, ch14.18, is the only anti-GD2 antibody to be evaluated in a large controlled clinical trial, in which it demonstrated overall survival of 86% at 2 years in patients with high-risk neuroblastoma. Older nonrandomized studies of ch14.18 monotherapy and 3F8, a murine antibody, suggest this survival rate remains between 50 and 85% at 5 years posttreatment.
  
  
  CONCLUSIONS
  Multiple GD2-specific monoclonal antibodies have been researched over the last decade in patients diagnosed with high-risk neuroblastoma. One anti-GD2 antibody, ch14.18, was found to significantly improve event-free and overall survival of high-risk neuroblastoma. Therefore, the standard approach to treating high-risk neuroblastoma is likely to undergo a major shift once an anti-GD2 antibody becomes commercially available.
authors: Department of Pharmacy, Children's of Alabama, Birmingham, AL, USA. kerry.parsons@childrensal.org
authors: Kerry
authors: K
authors: Parsons
authors: Brooke
authors: B
authors: Bernhardt
authors: Brandy
authors: B
authors: Strickland
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002986:Clinical Trials as Topic; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005732:Gangliosides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D012306:Risk; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D005732:Gangliosides; C025447:sialogangliosides