Complete Tumor Ablation With Iodine 131-Radiolabeled Disialoganglioside GD2-Specific Monoclonal Antibody Against Human Neuroblastoma Xenografted in Nude Mice23

Abstract

The antibody 3F8, an IgG3 murine monoclonal antibody (MoAb) against disialoganglioside GD2, could target iodine-131 (131I) to established subcutaneous human neuroblastoma (NB) xenografts in BALB/c nude mice. 131I-radiolabeled MoAb (0.125-1 mCi) was injected iv. Tumor radioactivity over time was calculated from scintigraphy, and radiation dose to individual tumors was calculated. Tumor shrinkage occurred only with 131I-labeled 3F8, but not with nonradioactive 3F8 or radiolabeled irrelevant antibody. While the tumor of the control mice enlarged by tenfold, the treated tumor showed over 95% shrinkage by 12 days. Both the rate of shrinkage and duration of tumor response were dose dependent. Calculated doses of more than 10,000 rad could be achieved. Only those tumors that received more than 4,200 rad were completely ablated without recurrence. Recurrent tumors were not antigen negative or radioresistant. These results confirmed the prediction based on imaging studies that human NB xenografts could be effectively eradicated with the use of 131I-labeled MoAb 3F8 with tolerable toxicities.

Immunolocalisation and imaging of small cell cancer xenografts by the IgG2a monoclonal antibody SWA11

“…RIT has shown variable success in the treatment of human tumour xenografts grown in rodent models. In one study complete ablation of a radiosensitive neuroblastoma has been reported (Cheung et al, 1986) but other reports show a high dependency on the age of the tumour, with only limited inhibition of growth in those which are well established (Epenetos, 1984;Badger et al, 1986;Sharkey et al, 1987). In view of the high localising capacity of SWAl1, its persistence at the tumour, its accompanying low blood and normal tissue levels and the inherent radiosensitivity of SCC we are now encouraged to examine the efficacy of SWAl1 as a radioimmunotherapeutic agent in our xenograft model system.…”

The selection of antibodies for targeted therapy of small-cell lung cancer (SCLC) using a human tumour spheroid model to compare the uptake of cluster 1 and cluster w4 antibodies

“…Studies in animals with human tumour xenografts have demonstrated that the most favourable anti-tumour antibody uptake ratio is seen in small tumours (Rogers et al, 1986;Pedley et al, 1987), and this probably accounts for the good results of radioimmunotherapy in these animals (Cheung et al, 1986;Buchegger et al, 1989;Smith et al, 1991). In man radiolabelled antibodies have usually been given to treat large tumours, and although responses occur they are rarely sustained.…”

Monoclonal antibody 3F8 recognises the neural cell adhesion molecule (NCAM) in addition to the ganglioside GD2

“…GD2 for example is present on human brain, but found in much higher amounts on melanoma and neuroblastoma tissues (Cahan et al, 1982;Schultz et al, 1984). Antibodies such as 3F8, recognised the GD2 ganglioside Saito et al, 1985), have been used for radioimmunoscintigraphy studies (Cheung et al, 1986;Miraldi et al, 1986), and phase 1 clinical trials (Cheung et al, 1987). Melanoma and neuroblastoma patients have been given 3F8, either alone or conjugated to 131I and some clinical responses have been noted.…”