title: A phase I/IB trial of murine monoclonal anti-GD2 antibody 14.G2a plus interleukin-2 in children with refractory neuroblastoma: a report of the Children's Cancer Group.
abstract: BACKGROUND
  The murine monoclonal antibody (MoAb) 14.G2a recognizes GD2, a disialoganglioside expressed in tumors of neuroectodermal origin, and facilitates antibody dependent cellular cytotoxicity (ADCC) in vitro. When given in vivo, interleukin-2 (IL-2) can increase ADCC by enhancing the activity and number of circulating lymphocytes.
  
  
  METHODS
  Thirty-three pediatric patients with GD2 positive malignancies, ranging in age from 2 to 17 years (median, 9.9 years), received IL-2 and 14.G2a in this Phase I/IB study of the Children's Cancer Group (CCG) and were monitored for toxicities and response to therapy. Seven of these patients also received granulocyte-macrophage-colony stimulating factor.
  
  
  RESULTS
  The maximum tolerated dose (MTD) of 14.G2a with IL-2 was 15 mg/m2/day. The most prevalent Grade 3-4 toxicities were generalized pain (n = 14 [42%]) and fever without documented infection (n = 17 [52%]). IL-2 was thought to be the causative agent in most cases of fever. Toxicities attributed to 14.G2a included pain, allergic or anaphylactic reactions, and rash. Human antimouse antibodies were demonstrated in 9 of 21 evaluated patients. One patient with neuroblastoma had a partial response, and one patient with osteosarcoma had a complete response. Immunocytology demonstrated that the number of neuroblastoma cells in bone marrow decreased in three patients.
  
  
  CONCLUSIONS
  The murine MoAb 14.G2a was well tolerated at the MTD and appeared to have some antitumor activity. Further development of this approach will involve additional engineered forms of the antibody as well as testing in the adjuvant and minimal residual disease setting.
authors.affiliation: University of Wisconsin, Madison, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Frost
authors.forename: J A
authors.initials: JA
authors.lastname: Hank
authors.forename: G H
authors.initials: GH
authors.lastname: Reaman
authors.forename: S
authors.initials: S
authors.lastname: Frierdich
authors.forename: R C
authors.initials: RC
authors.lastname: Seeger
authors.forename: J
authors.initials: J
authors.lastname: Gan
authors.forename: P M
authors.initials: PM
authors.lastname: Anderson
authors.forename: L J
authors.initials: LJ
authors.lastname: Ettinger
authors.forename: M S
authors.initials: MS
authors.lastname: Cairo
authors.forename: B R
authors.initials: BR
authors.lastname: Blazar
authors.forename: M D
authors.initials: MD
authors.lastname: Krailo
authors.forename: K K
authors.initials: KK
authors.lastname: Matthay
authors.forename: R A
authors.initials: RA
authors.lastname: Reisfeld
authors.forename: P M
authors.initials: PM
authors.lastname: Sondel
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology*; D009447:Neuroblastoma / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007376:Interleukin-2; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C019403:ganglioside, GD2