Abstract
Local administration of radioimmunoconjugates may allow successful tumor therapy. Bladder cancer appears well suited to this approach, because of its superficial and multifocal nature, and because it will allow direct intravesical administration of conjugates. Implantation of human bladder cancer cell lines in the bladder wall of nude rats results in tumor formation, providing an excellent model to test this. We have developed two murine monoclonal antibodies (MAbs), BLCA-8, IgG3, and BLCA-38, IgG1, both of which react with malignant cells and shed into voided urine of patients with transitional cell carcinoma (TCC) of the bladder, but not with normal bladder urothelial cells. Radioimmunoconjugates produced with131Iodine (131I) or125I have been used for biodistribution studies following administration directly into the bladder. Radioiodinated intact MAbs or Fabs administered intravesically into nontumor-bearing rats did not leak into the systemic circulation and were stable in urine for up to 100h. Biodistribution studies carried out following intraperitoneal or intravesical administration of radioimmunoconjugates to tumor-bearing nude rats indicate good tumor uptake of both MAbs. Together with immunoreactivity assays, these studies demonstrate that131I-labeled MAbs have considerable potential for intravesical radioimmunotherapy of human bladder tumors, and further studies are under way.
Similar content being viewed by others
References
Silverberg E., Boring C. C., and Squires T. S. (1990)Cancer Statistics,40, 9–26.
Raghavan D., Shipley W. U., Garnick M. B., Russell, P. J., and Richie, J. P. (1990) Biology and management of bladder cancer: advances and innovations.N. Engl. J. Med. 322, 1129–1138.
Bander N. H. (1987) Monoclonal antibodies in urologic oncology.Cancer 60, 658–667.
Dotsikas G., Konowalchuk T., Major P. P., Kovac, P. E., Ward, G. K., Stewart, S. S., Price, G. B., Elhilali, M. M., and Mackillop, W. J. (1987) Cellular heterogeneity in normal and neoplastic human urothelium: a study using murine monoclonal antibodies.Br. J. Cancer 56, 439–444.
Russell, P. J., Ho Shon, I., Boniface, G. R., Bard, M. E., Philips, J., Raghavan, D., and Walker, K. Z. (1991) Growth and metastasis of human bladder cancer xenografts in the bladder of nude rats. A model for intravesical immunotherapy.Urol. Res. 19, 207–213.
Walker K. Z., Russell P. J., Kingsley E. A., Philips, J., and Raghavan, D. (1989) Detection of malignant cells in voided urine from patients with bladder cancer, a novel monoclonal assay.J. Urol. 142, 1578–1583.
Lightfoot, D. V., Walker, K. K., Boniface, G. R., Hetherington, E. L., Izard, M. E., and Russell, P. J. (1991) Dosimetric and therapeutic studies in nude mice xenograft models with153Samarium-labeled monoclonal antibody, BLCA-38.Antibody Immunoconjugates and Radiopharmaceuticals 4, 319–330.
Russell, P. J., Jelbart, M., Wills, E. J., Singh, S., Wass, J., Wotherspoon, J., and Raghavan, D. (1988) Establishment and characterization of a new human bladder cancer cell line showing features of squamous and glandular differentiation.Int. J. Cancer 41, 74–82.
Brown, J., Russell, P. J., Philips, J., Wotherspoon, J., and Raghavan, D. (1990) Clonal analysis of a bladder cancer cell line: an experimental model of tumour heterogeneity.Br. J. Cancer 61, 369–376.
Chen, T. R. (1977)In situ detection of Mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain.Exp. Cell Res. 104, 255–262.
Russell P. J., Raghavan D., Gregory P., Philips, J., Wills, E. J., Jelbart, M., Wass, J., Zbroja, R., and Vincent, P. C. (1986) Bladder cancer xenografts: a model of tumor cell heterogeneity.Cancer Res. 46, 2035–2040.
Russell, P. J., Boniface, G. R., Izard, M. E., Lightfoot, D. V., Gansow, O., Brechbiel, M., Raghavan, D., and Walker, K. Z. (1990) Development of animal models to assess radioimmunoconjugates for the treatment of bladder cancer. Proceedings of International Conference on Treatment of Melanoma and Other Cancers, Sept. 1990, Newcastle, NSW.
Britton, W. J., Hellquist, L., Basten, A., and Raison, R. L. (1985)M. leprae antigens involved in human immune responses.J. Immunol. 135, 4171–4177.
Walker K. Z., Seymour-Munn K., and Keech F. K. (1986) A rat model system for radioimmunodetection ofkappa myeloma antigen on malignant B cells.Eur. J. Nucl. Med. 12, 461–467.
Brechbiel, M. W. and Gansow, O. A. (1991) Backbone-substituted DTPA ligands for90Y radioimmunotherapy.Bioconjugate Chem. 2, 187–194.
Lindmo, T., Boven, E., Cuttitta, F., Fedorko, J., and Bunn, P. A. (1984) Determination of immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess.J. Immunol. Meth. 72, 77–79.
Goldenberg, D. (1988) Targeting of cancer with radiolabeled antibodies: prospects for imaging and therapy.Arch. Pathol. Lab. Med. 112, 580–586.
Riva, P., Marangolo, S., Lazzari, M., Agostini, M., Sarti, G., Moscatelli, G., Franceschi, G., Spinelli, A., and Vechhietti, G. (1989) Locoregional immunotherapy of human ovarian cancer: preliminary results.Nucl. Med. Biol. 16, 659–666.
Boekmann, W., Baum, R. P., Schuldes, H., Kramer, W., Hertel, A., Baew-Christow, T., Hanke, P., Jonas, D., and Hor, G. (1990) Tumour imaging of bladder carcinomas and their metastases with111indium-labelled monoclonal anti-CEA antibody BW 431/26.Br. J. Cancer 62, Suppl. X, 81–84.
Epenetos, A. A., Snook., D., Durbin, H., Johnson, P. M., and Papdimitriou, J. (1986) Limitations of monoclonal antibodies for localization of human neoplasms.Cancer Res. 46, 3183–3191.
Colcher, D., Esteban, J., Carrasquillo, J. A., Sugarbaker, P., Reynolds, J. C., Bryant, G., Larson, S. M., and Schlom, J. (1987) Complementation of intracavitary and intravenous administration of a monoclonal antibody (B72.3) in patients with carcinoma.Cancer Res. 47, 4218–4224.
Epenetos, A. A., Munro, A. J., Stewart, S., Rampling, R., Lambert, H. G., McKenzie, C. G., Soutler, P., Rachemtulla, A., Hooker, G., Sivolapenka, G. B., Snook, D., Courtney-Luck, N., Dhokia, B., Krausz, T., Taylor-Papadimitriou, J., and Bodmer, W. F. (1987) Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies.J. Clin. Oncol. 5, 1890–1899.
Hnatowich, D. J., Chinol, M., Siebecker, D. A., Gionet, M., Griffin, T., Doherty, P. W., Hunter, R., and Kase, K. R. (1988) Patient biodistribution of intraperitoneally administered Yttrium-90-labeled antibody.J. Nucl. Med. 29, 1428–1434.
Wahl, R. L. and Liebert, M. (1989) Improved radiolabeled monoclonal antibody uptake by lavage of intraperitoneal carcinomatosis in mice.J. Nucl. Med. 30, 60–65.
Griffin, T. W., Collins, J., Bokhari, F., Stochl, M., Brill, A. B., Ito, T., Emond, G., and Sando, H. (1990) Intraperitoneal immunoconjugates.Cancer Res. 50, 1031–1038.
Newling, D. (1990) Intravesical therapy in the management of superficial transitional cell carcinoma of the bladder: the experience of the EORTC GU group.Br. J. Cancer 61, 497–499.
Bamias A., Keane, P., Krausz, T., Williams G., and Epenetos, A. A. (1991). Intravesical administration of radiolabeled antitumor monoclonal antibody in bladder carcinoma.Cancer Res. 51, 724–728.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Russell, P.J., Plomley, J., Shon, I.H. et al. Monoclonal antibodies for intravesical radioimmunotherapy of human bladder cancer. Cell Biophysics 22, 27–47 (1993). https://doi.org/10.1007/BF03033865
Issue Date:
DOI: https://doi.org/10.1007/BF03033865