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Promising results of a
pilot trial of a GD2 directed anti-idiotypic antibody as a vaccine
for high risk neuroblastoma
A. Batova, A. L. Yu, D. Strother, P. Angelini, A. Eskenazi
UCSD, San Diego, CA; University of Calgary, Calgary, AB, Canada;
University of Turin, Turin, Italy; University of Maryland, Baltimore, MD
Background.
High risk neuroblastoma has a dismal outcome despite
intensive therapy including stem cell transplant.
We conducted the first pediatric trial of mAb1A7, an anti-id antibody directed
against anti-GD2, 14G2a, as a vaccine for high risk neuroblastoma.
Methods.
Thirty one patients with high risk neuroblastoma (26 stage 4, 5
stage 3) who achieved first or subsequent complete response (16 in CR1, 7 in
CR2) or very good partial response (3 in VGPR1, 5 in VGPR2) were entered into
this trial.
Patients received SQ injection of mAb1A7 (Titan Pharmaceutical Inc.) + QS-21
(Aquila Pharmaceutical Inc.) q2 weeks x 4, q m x 11.
Results.
The treatment was well tolerated with only transient local
reactions, transient fever and chills in 4 patients and serum sickness in
1.
There was no neuropathic pain which is often seen with infusion of
anti-GD2.
Despite prior intensive treatment including stem cell transplantation in all but
4 patients, all 31 patients generated anti-mAb1A7.
The mean peak anti-mAb1A7 was 665 ± 390 ng /ml (83-1467).
Anti-mAb1A7 inhibited the binding of mAb1A7 (Ab2) to 14G2A (Ab1) in 31/31.
The peak inhibition was observed between weeks 22 and 62, at which time, immune
sera from 14/31 patients inhibited binding of Ab2 to Ab1 by > 90% at
a 160- fold dilution.
Immunoaffinity purified Ab3 from 5/5 patients bound purified GD2 and was
predominantly IgG.
More importantly, immune sera from 9/13 patients tested after 37 weeks of
treatment, displayed CDC activity.
Furthermore, purified Ab3 from 6/8 patients mediated ADCC against
neuroblastoma.
To date, 17 of 20 patients who enrolled during first remission have no evidence
of disease progression at 32+ to 52+ months (median + 47 m) from study entry,
while only 1 of 11 patients who enrolled during 2nd remission remains
progression free.
Conclusions.
mAb1A7 + QS21 is safe and effective in inducing biologically
active anti-GD2 in heavily pre-treated neuroblastoma patients and may be useful
in controlling minimal residual disease.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-001309,00.asp
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