Target-cell cytotoxicity of a hybrid of Fab' on immunoglobulin and A-chain of ricin.

As an approach to the development of new antitumor agents, a hybrid in which one molecule of the Fab' fragment of a rabbit anti-murine leukemia L1210 immunoglobulin G (IgG) was linked to the A-chain of ricin via a disulfide bone was prepared by the reaction of A-chain having one reactive thiol group with Fab' having one activated cysteine residue, followed by chromatography on Sephadex G-150 superfine. The hybrid exhibited a potent cytotoxicity towards L1210, whereas unconjugated Fab', unconjugated A-chain, or an equimolar mixture of the two showed no significant cytotoxicity. Furthermore, the hybrid with Fab' of normal IgG had no cytotoxicity towards L1210 cells. The results indicate that the hybrid manifests its toxic activity towards the target cells through binding of its Fab' moiety of cell surface antigens.