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Abstract
In spite of the satisfactory frequency of clinical response to first-line therapy
in neuroblastoma (NB), complete eradication of NB cells is rarely achieved. As a consequence,
the majority of patients with advanced stage NB undergo relapse, which is often resistant
to conventional treatment and rapidly overwhelming. Thus, after induction of the apparent
remission, new therapeutic strategies are needed to completely eradicate the small
number of surviving NB cells and to prevent relapse. We explored the potential of
different doses of the anti-GD2 monoclonal antibody (mAb) 14G2a in an experimental
metastatic model where a limited number of HTLA-230 human NB cells are injected i.v.
into nude mice, leading to extensive metastases and death of animals within 7-8 weeks.
Treatment with 14G2a mAb (1-4 mg/kg cumulative dose given as five i.v. daily administrations)
dramatically reduced the metastatic spread of NB cells and prolonged the long-term
survival of treated mice in a dose-dependent manner. Neither macrophages nor NK cells
appeared to contribute to the protective effect of antibody treatment in vivo, suggesting
either an involvement of granulocytes or a complement-mediated cytotoxicity towards
NB cells. Whatever the effecting mechanism(s) involved, these results strongly support
the clinical use of anti-GD2 mAbs after first-line induction regimens.