Ullén A, Sandström P, Ahlström K R, Sundström B, Nilsson B, Arlestig L, Stigbrand T
Department of Immunology, University of Umeåa, Sweden.
Cancer Res. 1995 Dec 1;55(23 Suppl):5868s-5873s.
A syngeneic, high-affinity, anti-idiotypic monoclonal antibody (MAb; alpha TS1) raised against an anticytokeratin monoclonal antibody (TS1) was evaluated as a second antibody to promote the rapid clearance of radiolabeled TS1 from the blood during experimental radioimmunolocalization. By using a novel biosensor technology (BIAcore), association rate dissociation rate, and affinity constants between the idiotype and the anti-idiotype could be determined. The in vivo results in nude mice carrying HeLa Hep 2 tumors demonstrate the possibility of selectively regulating the amount of the idiotypic 125I-labeled circulating MAb by in vivo injection of this high-affinity, anti-idiotypic antibody. Injection of the anti-idiotype in a molar ratio of 0.75 to the idiotype cleared the blood pool from circulating radiolabeled idiotype within 24 h, with a concomitant rapid excretion of 125I in urine. The total amount of remaining radioactivity in the animals decreased to 15-20% during these 24 h, with the tumors still retaining 60-65% of their initial radioactivity. This approach, using syngeneic primary and secondary MAbs with minimized immunogenicity, significantly improves the tumor:nontumor ratio, thus improving efficiency in experimental radioimmunolocalization and radioimmunotherapy, leaving the endogenous antibody repertoire of the host unaffected.
