K. Kramer et al., DISIALOGANGLIOSIDE G(D2) LOSS FOLLOWING MONOCLONAL-ANTIBODY THERAPY IS RARE IN NEUROBLASTOMA, Clinical cancer research, 4(9), 1998, pp. 2135-2139
Ganglioside G(D2) is abundant on human neuroblastoma (NB). Monoclonal
antibody 3F8 targeted to G(D2) may have imaging and therapeutic potent
ial. Antigen-negative clones can escape immune-mediated attack, leadin
g to clinical resistance or recurrence. Among 95 evaluable patients tr
eated i.v. with 3F8 (94 stage 4 and 1 stage 3), 66 received nonradiola
beled 3F8, II received I-131-labeled 3F8 (8-28 mCi/kg) with autologous
hone marrow rescue, and 18 received bath forms of treatment, Prior to
treatment, 91 patients tested positive for G(D2) reactivity by bone m
arrow immunofluorescence (n = 68), tumor immunohistochemistry (n = 20)
, or diagnostic radioimmunoscintigraphy only (il = 3), Of 62 patients
who had refractory or recurrent NB following 3F8 treatment, 61 (98%) t
ested positive for G(D2) reactivity by bone marrow immunofluorescence
(II = 51) or tumor immunohistochemistry (rt = 10), The sole tumor that
lost G(D2) expression underwent phenotypic transformation into a pheo
chromocytoma-like tumor. The persistence of G(D2) expression in refrac
tory or recurrent NE suggests that complete antigen loss is an uncommo
n event and cannot account for treatment failure.