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.