title: Disialoganglioside G(D2) loss following monoclonal antibody therapy is rare in neuroblastoma.
abstract: Ganglioside GD2 is abundant on human neuroblastoma (NB). Monoclonal antibody 3F8 targeted to GD2 may have imaging and therapeutic potential. Antigen-negative clones can escape immune-mediated attack, leading to clinical resistance or recurrence. Among 95 evaluable patients treated i.v. with 3F8 (94 stage 4 and 1 stage 3), 66 received nonradiolabeled 3F8, 11 received 131I-labeled 3F8 (8-28 mCi/kg) with autologous bone marrow rescue, and 18 received both forms of treatment. Prior to treatment, 91 patients tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 68), tumor immunohistochemistry (n = 20), or diagnostic radioimmunoscintigraphy only (n = 3). Of 62 patients who had refractory or recurrent NB following 3F8 treatment, 61 (98%) tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 51) or tumor immunohistochemistry (n = 10). The sole tumor that lost GD2 expression underwent phenotypic transformation into a pheochromocytoma-like tumor. The persistence of GD2 expression in refractory or recurrent NB suggests that complete antigen loss is an uncommon event and cannot account for treatment failure.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kramer
authors.forename: W L
authors.initials: WL
authors.lastname: Gerald
authors.forename: B H
authors.initials: BH
authors.lastname: Kushner
authors.forename: S M
authors.initials: SM
authors.lastname: Larson
authors.forename: M
authors.initials: M
authors.lastname: Hameed
authors.forename: N K
authors.initials: NK
authors.lastname: Cheung
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D005732:Gangliosides / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D008297:Male; D009447:Neuroblastoma / Q000378:metabolism* / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D005732:Gangliosides; C019403:ganglioside, GD2