MAb B72.3, a murine IgG1, has been shown to react with a high molecular weight glycoprotein (designated TAG-72) found in many epithelial-derived cancers, with minimal reactivity to normal adult tissues. B72.3 was, therefore, chosen as an antibody that could potentially be used for radioimmunodetection and radioimmunotherapy of human carcinomas and is being evaluated in model systems using the LS-174T human colon carcinoma xenograft to determine the feasibility of these studies A number of new chelate-conjugates have been developed enabling the binding of radiometals to proteins. These new constructs have been covalently linked to B72.3 IgG to determine which resulted in the best biodistribution after labeling with In-Ill and Y-88 (used as a substitute for Y-90). Dose fractionation studies were carried out and demonstrated that splitting the dose of a radiolabeled MAb for therapy can reduce toxicity and increase efficacy. A recombinant/chimeric form of B72.3 has been developed using the variable regions of the murine B72.3 and human heavy chain and light chain constant regions. New anti-TAG-72 MAbs (designated CC) have been developed and compared to B72.3 in the LS-174T model system. All exhibited higher %ID/gm and tumor:tissue ratios than B72.3; differences in the pharmacokinetics were noted among the CC MAbs. Tumor targeting and pharmacokinetic studies were also carried out using a genetically engineered single chain antigen binding protein (sFv). These studies demonstrated that a relatively small (27kD) single chain molecule can efficiently target a human tumor xenograft.
