Bispecific Monoclonal Antibodies for the Targeting of Type I Ribosome-Inactivating Proteins Against Hematological Malignancies

Monoclonal antibodies (MAbs) recognizing tumor-associated antigens (TAA) have been widely used to selectively deliver toxic compounds to neoplastic cells. In most studies, tumor targeting was achieved by the use of immunotoxins (IT) generated by chemical conjugation of an antibody to a toxin (1 ). In addition, several recombinant antibody-toxin chimeric molecules have been generated by genetic engineering (2 ). Ricin A-chain, which enzymatically damages ribosomal RNA, has been most commonly used for the generation of ITs, although several other single-chain ribosome-inactivating proteins (RIPs) or type I RIPs are also available (3 ). Type I RIPs are RNA N -glycosidases displaying potent inhibition of protein synthesis in cell-free assays, but they lack a lectin B-chain for cell entry, and thus have a low toxicity for whole cells. Type I RIPs such as saporin can be easily purified (4 ) and have been successfully used to generate potent ITs, displaying antitumor activity both in vitro (5 ) and in vivo (6 ).