Anti-GD2 monoclonal antibody immunotherapy: a promising strategy in the prevention of neuroblastoma relapse.
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.
Raffaghello
L
L
Laboratory of Oncology, G. Gaslini Children's Hospital, Largo G. Gaslini 5, 16148 Genoa, Italy. lizziaraffaghello@ospedale-gaslini.ge.it
Marimpietri
D
D
Pagnan
G
G
Pastorino
F
F
Cosimo
E
E
Brignole
C
C
Ponzoni
M
M
Montaldo
P G
PG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D009447:Neuroblastoma / Q000517:prevention & control / Q000628:therapy*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D005732:Gangliosides; C019403:ganglioside, GD2