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 (RID) and radioimmunotherapy (RIT) 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-111 and Y-88 (used as a substitute for Y-90). The 1-(p-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid (SCN-Bz-DTPA) chelate-conjugate, gave the best biodistribution after labeling with either In-111 or Y-88. The biodistribution of the Y-88 and In-111 labeled MAbs differed significantly, illustrating the difficulties in using In-111-labeled MAbs to predict the distribution and dosimetry of Y-90-- labeled MAbs. 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. A recombinant/chimeric form of B72.3 has been developed using the variable regions of the murine B72.3 and human heavy chain (gamma 4) and light chain (kappa) constant regions. The cB72.3(gamma 4) IgG was radiolabeled and the biodistribution was studied in athymic mice bearing LS-174T xenografts. Small differences were observed between the cB72.3(gamma 4) and the native B72.3 in the %ID/gm that localized in the tumor, this is mostly likely due its more rapid clearance from the blood and body of the mouse of the cB72.3(gamma 4) as compared to the native B72.3.
