Monoclonal antibodies B6.2 and B72.3 bind to human breast and colon tumor associated antigens. IgG from both these monoclonal antibodies was purified and F(ab')2 and Fab' fragments were prepared from the B6.2 IgG. The B72.3 IgG and B6.2 IgG and fragments were radiolabeled with I-125 and I-131 without loss of their immunoreactivity. The radiolabeled antibodies and fragments were injected into athymic mice bearing antigen positive human breast or colon tumors or an antigen-negative melanoma as a negative control. The B6.2 IgG and fragments localized specifically in the breast tumor xenografts with the IgG giving maximal activity in the tumor. The F(ab')2 fragment gave the best tumor-to-normal tissue ratios (15-20:1 for liver and spleen) due to its rapid clearance from the blood stream. The Fab' fragment cleared more rapidly than the F(ab')2 or the intact IgG with the majority of the radioactivity in the kidneys. When radiolabeled B72.3 IgG was injected into mice bearing colon carcinoma xenografts activity in the tumor rose from the first 2 days and remained constant over the 19 day period of study. Tumor-to-normal tissue ratios rose over this period of time with ratios of approximately 18:1 for liver, spleen and kidney at 7 days. At 19 days approximately 40% of the radiolabeled B72.3 IgG was found in the tumor. Model systems that resemble the metastatic nature of human colon carcinomas are being developed to better determine the efficacy of radiolabeled monoclonal antibodies as potential agents for radioimmunodetection and radioimmunotherapy.
NIH ExPorter
NIH ExPorter