P1-01-01: A Rat Monoclonal Antibody Against Bone Sialoprotein II Is Active in Preventing and Treating Tumor Growth and Osteolytic Lesions in Nude Rats Induced by MDA-MB-231 Breast Cancer Cells.
Authors: MR Berger, M Zepp, FP Armbruster
Journal: Cancer Research (2011)

Abstract The SIBLING protein bone sialoprotein II (BSPII) has been found implicated in lytic skeletal metastasis. Previous experiments had shown that targeting BSPII by a polyclonal IgY antibody or knock down of the gene's transcript are instrumental in inhibiting experimental lytic skeletal metastasis. The aim of this study was to investigate the preventive and therapeutic effects of a new rat monoclonal anti BSPII antibody against tumor growth and osteolytic activity of MDA-MB-231 breast cancer cells growing in nude rats. In the preventive arm of this study, rats were pre-treated with the antibody (0 and 10 mg/kg) starting one week before tumor inoculation. In parallel, MDA-MB-231luc cells were incubated with the antibody for one week (0 and 0.5 mg/ml). Following inoculation of 1×105 MDA-MB-231luc breast cancer cells into the femoral artery of 6 male nude rats, respectively, lesions were expected to develop only in the tibia, femur or fibula of the respective hind leg. Their appearance and development were monitored for six weeks by light emission, caused by luciferase mediated metabolism of luciferin. Photon emission was recorded at regular intervals by a Xenogen IVIS 100 imaging system. In the treatment arm of this study, the antibody administration (10 mg/kg/week) started when tumor bearing rats had shown stable tumor growth. Experimental groups of rats received the first treatment either at four (late onset; n = 8) or at two (early onset; n = 6) weeks after tumor cell implantation. Tumor bearing animals were (sham-) treated and followed for up to 8 weeks. All 6 control rats of the preventive arm showed steady tumor growth. In variance, the rats receiving MDA-MB-231luc cells that had been pre-exposed to the antibody and those rats, which had been pre-treated with the antibody showed clearly reduced light emission as indicator of reduced tumor growth. At 6 weeks after tumor cell inoculation, only 1 of 6 rats was positive for light emission in the group receiving pre-exposed tumor cells (p&amp;lt;0.01), 3 of 6 rats were positive in the group receiving pre-treatment with the antibody (p&amp;lt;0.05), and 1 of 6 rats was positive in the group receiving both, pre-exposed tumor cells as well as pre-treatment with the antibody (p&amp;lt;0.01). In the treatment arm, all but one untreated tumor bearing rats showed rapid tumor growth accompanied with lytic destruction of femur and tibia of the respective hind leg (18/19; tumor take rate 95%). In contrast, rats treated with the anti-BSP antibody did not show a significant increase in light emission nor a clinical deterioration. In fact, 6 of 8 rats receiving the late onset therapy didn't show any light emission after 4 to 6 weeks (p = 0.01 versus control) as well as 4 of 6 rats receiving the early onset therapy with the antibody (p &amp;lt; 0.05). Radiological and histological examination confirmed that animals without light emission were free of tumor growth, corresponding to a complete remission. In conclusion, the rat monoclonal antibody directed against BSP II is a powerful tool in treating experimental skeletal metastasis and warrants further development. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-01.