This project involves the use and the proposed use of several monoclonal antibodies (MAbs) in both diagnostic and therapeutic clinical trials. Thus far, all our collaborative clinical trials have been conducted with MAb B72.3. This MAb has been previously shown to have differential reactivity for a range of human carcinomas as compared to most normal adult tissues. To date, over 1,000 patients have been administered radiolabeled B72.3 in tumor-targeting studies carried out in several institutions, with similar findings of approximately 7080% tumor targeting observed. We first investigated the administration of radiolabeled MAb B72.3 IgG in colorectal cancer patients. The selective localization of (131)I-MAb B72.3 IgG was demonstrated in biodistribution studies in which the percentage of injected dose of MAb per gram of each tumor was compared with that of the normal tissues, thus providing a relative radiolocalization index (RI) for each lesion. Of the tumor lesions, 70% had an RI of at least 3 (i.e., 3 times greater uptake per gram than normal tissues). We have also conducted studies to determine the feasibility of intraperitoneal administration of radiolabeled B72.3 for tumor localization (via both gamma scanning and direct analyses of biopsy specimens). Several patients studied were negative for tumor detection by both CT scan and X-ray but were positive for tumor localization via gamma scanning. Direct analyses of biopsy specimens of carcinoma and normal tissues demonstrated ratios ofup to 70:1 for tumor MAb localization versus normal tissues. A phase I therapy trial involving intraperitoneal administrationof (131) I-B72.3 IgG in patients with ovarian or colorectal carcinoma confined to the peritoneal cavity is in progress. The use of recombinant/chimeric MAbs has also begun and other MAb-isotope conjugates are planned.
