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Antibody-dependent
cellular cytotoxicity (ADCC) in COG ANBL0032: A phase III randomized trial of
chimeric anti-GD2 and GM-CSF/IL2 in high risk neuroblastoma following
myeloablative therapy and autologous stem cell transplant (ASCT)
A. L. Yu, A. Batova, R. Gribi, M. Diccianni, L. Bridgeman, D. Geske, W.
London, A. Gilman, F. Ozkaynak
UCSD, San Diego, CA; University of Edinburgh, Edinburgh, United
Kingdom; COG, Gainesville, FL; COG, Arcadia, CA
Background.
ADCC plays an important role in the efficacy of anti-cancer
monoclonal antibody therapy.
We monitored ADCC activities of neuroblastoma patients enrolled on COG
ANBL0032.
Methods.
High risk neuroblastoma patients who achieved a complete or very
good partial response after induction therapy, myeloablation with carboplatin +
etoposide + melphalan, ASCT, and local radiation according to COGA3973, were
eligible for this study.
After engraftment, they were randomized to 13-cis-retinoic acid (RA) x 6 courses
or RA + immunotherapy with 5 courses of Ch14.18 and alternating cycles of GM-csf
and IL2.
Results.
So far, 27 patients have been evaluated before treatment on day
76 ± 9 (62~93) post-ASCT.
The mononuclear cells of all 27 patients displayed ADCC which averaged 43.2 ±
28.3 LU20 (11.7~138).
Granulocytes of all 23 patients evaluated pre-treatment also showed ADCC with an
average of 18.7 ± 17.9 LU20 (3.4~67.5).
ADCC of both cell types were significantly less than that observed for 5 normal
donors who had a mean of 145.7 ± 58.3 LU20 (P=0.001) for mononuclear
cells and 26.7 ± 7.1 (P=0.0168) for granulocytes.
ADCC mediated by both cell types in patients did not change significantly
subsequently: before 4th course of RA/ immunotherapy on day 163, and
before last course of RA/ immunotherapy on day 196.
Although impaired chemotaxis of granulocytes has been reported during IL-2
therapy, we found no significant changes in granulocyte mediated ADCC, right
before and after ch14.18 + IL2.
Conclusions.
These findings suggest that ADCC mediated by mononuclear
cells and granulocytes are present shortly after ASCT and persist throughout the
course of immunotherapy, albeit at lower levels than normal controls, which is
consistent with the reported decreased ADCC in cancer patients.
The preliminary findings so far indicated that there is residual ADCC following
ASCT, which may allow the monoclonal antibody to be efficacious.
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_19-001642,00.asp
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