Monoclonal antibodies for intravesical radioimmunotherapy of human bladder cancer

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 with 131Iodine (131I) or 125I 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 100 h. 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 that 131I-labeled MAbs have considerable potential for intravesical radioimmunotherapy of human bladder tumors, and further studies are under way.