Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents

To enhance the antitumor potential of soybean Bowman-Birk inhibitor (BBI), the conjugate of BBI with an antibody via a macromolecular carrier was prep ared. Clinical dextran (D) was used as a biocompatible biodegradable carrie r for co-immobilization of BBI and antibody. A model immunoglobulin isolate d from sheep serum (sIgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis. The molar ratio of the ingredi ents in the conjugate was the following BBI:D:sIgG=9:1:1. Comparison of the dose response curves for the native sIgG and the BBI-D-sIgG conjugate indi cated that sIgG completely retained its specific activity (> 90%) after mod ification with dextran. The determination of the K-i values for chymotrypsi n interaction with the native BBI and the BBI-D-sIgG conjugate indicated hi gh anti-chymotrypsin activity. In the next step, the monoclonal antibody (I CO 25 MAb) against the mucin-like human epithelial membrane antigen was use d for conjugation as it is the most universal vector for targeting differen t agents to human tumors of epithelial origin. The influence of conjugation on the specificity of the Mab reaction with its antigen was studied. The c onjugated MAb reacted with tumor cells of different epithelial genesis (bre ast, lung, gastric, ovarian and uterus tumors), but did not react with tumo r cells of non-epithelial origin. It was shown that BBI-D-ICO 25 MAb conjug ate has almost the same immunohistochemical activity as non-conjugated MAb. These results demonstrated the feasibility of exploiting the activities of covalently bound BBI and ICO 25 MAb for anticarcinogenic agent targeting.