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Biodistribution, Binding and Internalisation of Monoclonal Antibodies to Human Ovarian Carcinoma Cells

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Part of the book series: Developments in Biotherapy ((DIBI,volume 1))

Abstract

The aim of this preclinical study was to investigate whether the monoclonal antibody OV-TL 3 might be useful for targeting ovarian cancer. Immunocytochemical studies on frozen sections showed intensive staining in > 90% (62/67) of primary as well as metastasized ovarian carcinomas. Slight cross-reactivity was observed with endocervical, oviductal epithelium as well as with lymphoid cells. Using immunoelectron microscopy the antibody stained a tumour cell surface antigen (OA3). No cross reactivity with the antibodies OC125 or MOv18 were found in inhibition studies on NIH:OVCAR:3 cells. The antigen could be quantified in tumour extracts or cyst fluids, but could not be traced in patient serum using a sandwich radio-immuno assay. The affinity constant was 1.4 x 10-9 M-1 as determined by Satchard analysis and displacement studies. Biodistribution studies with 125-I-labeled OV-TL 3 in athymic mice showed that tumour uptake with OV-TL 3 was significant higher than with OC125, and almost 7 times higher than with a non-specific control antibody (OV-TL 19). Radioiodinated F(ab’)2 fragments revealed a much faster clearance, a lower tumour uptake (ID%/g) but much better tumour/tissue ratios from 6.9 to 53. The attachment of OV-TL 3 to tumour cells and subsequent internalisation were studied with confocal laser scanning microscopy. Internalisation of the antibody was noticed upon long term incubation (>3 hours) in a considerable number of OVCAR:3 cells. The results suggest that OV-TL 3 might be a potent antibody for targeting label or immunotoxins to ovarian cancer cells.

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© 1990 Springer Science+Business Media Dordrecht

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Poels, L.G. et al. (1990). Biodistribution, Binding and Internalisation of Monoclonal Antibodies to Human Ovarian Carcinoma Cells. In: Crommelin, D.J.A., Schellekens, H. (eds) From Clone to Clinic. Developments in Biotherapy, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3780-5_9

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  • DOI: https://doi.org/10.1007/978-94-011-3780-5_9

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-5683-0

  • Online ISBN: 978-94-011-3780-5

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