Growth and metastasis of human bladder cancer xenografts in the bladder of nude rats. A model for intravesical radioimmunotherapy

Abstract

A potentially useful therapeutic approach to the treatment of human bladder cancer is intravesical therapy with radiolabelled monoclonal antibodies (MAbs). We have established an animal model to study this approach. Inoculation of cloned 2B8 cells derived from the human bladder cancer cell line, UCRU-BL-17, into the bladder wall of nude rats pre-irradiated with 900 rads, resulted in local tumour growth in 39/40 (97.5%) animals, with invasion or metastases to distant organs in 25% of cases. Both the bladder tumours and the metastases were morphologically similar to the original biopsy sample from which the cell line, UCRU-BL-17, was established. The cells were of human origin, as shown by expression of HLA antigens, Alu probing, and cytogenetic analysis. Preliminary studies indicated that i.p. injection of anti-human bladder cancer monoclonal antibody (MAb), BLCA-38, radiolabelled with either iodine 131 or samarium 153 (153Sm), resulted in tumour localisation, with tumour-to-blood ratios of 5.04 (131I), and 4.3 and 3.1 (153Sm) respectively. We now aim to examine the efficacy of the intravesical route for radioimmunotherapy in the nude rat model. This model will also serve for preclinical studies on the efficacy of systemically injected radioimmunoconjugates for control of metastatic growth.