In vivo targeting of human neuroblastoma xenograft by anti-GD2/anti-Fc gamma RI (CD64) bispecific antibody.
Antidisialoganglioside (GD2) monoclonal antibodies can target in vitro and in vivo neuroblastoma cells. However, their in vivo use is limited by the presence of high levels of circulating IgG which hamper the recruitment of effector cells through the high affinity Fc gamma RI (CD64). A bispecific Fab' x Fab' antiGD2/antiFc gamma RI antibody (7A4 bis 22), which binds outside the IgG binding site of Fc gamma RI, was therefore developed. This antibody binds both human GD2+ neuroblastoma and Fc gamma RI+ activated macrophages in vitro. It can localise a GD2 positive neuroblastoma xenografted on Nu/Nu mice. Scintigraphy tumour/muscle ratios showed that targeting with this antibody has an excellent selectivity for the tumour over normal tissues. Furthermore, although its whole body clearance is more rapid than that of the 7A4 parental antibody over the first 48 h, its selective tumour uptake is similar, as shown by immunoscintigraphy imaging. Thus, such a bispecific antibody may represent an efficient tool for in vivo therapy of neuroblastoma through its ability to recruit Fc gamma RI+ effector cells even in presence of circulating IgG and to bind concomitantly GD2+ tumour cells.
Michon
J
J
Service de Pédiatrie, Institut Curie, Paris, France.
Perdereau
B
B
Brixy
F
F
Moutel
S
S
Fridman
W H
WH
Teillaud
J L
JL
D000818:Animals; D018033:Antibodies, Bispecific / Q000493:pharmacokinetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D005732:Gangliosides; D017452:Receptors, IgG; C025447:sialogangliosides