The construction of a non-hindered ricin immunotoxin and its use as a chemotherapeutic agent

The synthesis of an antibody-ricin immunotoxin selectively cytotoxic for human leukemic cells harbored in immune deficient SCID mice provides a novel way of testing human leukemia treatment strategies via a mouse model (14, 6). The integrity of such an immunotoxin must maintain both protein molecules so that the specificity and toxicity will be preserved. Often times the conjugation of the monoclonal antibody to the toxin places, steric constraints on the binding sites of both molecules, thus rendering the conjugate less active (8). This proposal deals with the placement of peptide spacer linkages between the disulfide bond of the two protein moieties to alleviate steric hinderance and thus, facilitate the efficacy of the immunotoxin.