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 prepared. Clinical dextran (D) was used as a biocompatible biodegradable carrier for co-immobilization of BBI and antibody. A model immunoglobulin isolated from sheep serum (sIgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis. The molar ratio of the ingredients 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 indicated that sIgG completely retained its specific activity (>90%) after modification with dextran. The determination of the Ki values for chymotrypsin interaction with the native BBI and the BBI-D-sIgG conjugate indicated high anti-chymotrypsin activity. In the next step, the monoclonal antibody (ICO 25 MAb) against the mucin-like human epithelial membrane antigen was used for conjugation as it is the most universal vector for targeting different agents to human tumors of epithelial origin. The influence of conjugation on the specificity of the Mab reaction with its antigen was studied. The conjugated MAb reacted with tumor cells of different epithelial genesis (breast, lung, gastric, ovarian and uterus tumors), but did not react with tumor cells of non-epithelial origin. It was shown that BBI-D-ICO 25 MAb conjugate 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.
Gladysheva
I P
IP
Department of Chemistry, M. V. Lomonosov Moscow State University, Russia. gladysheva@enzyme.chem.msu.ru
Moroz
N A
NA
Karmakova
T A
TA
Nemtsova
E R
ER
Yakubovskaya
R I
RI
Larionova
N I
NI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001666:Binding Sites, Antibody; D002417:Cattle; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects / Q000276:immunology; D011108:Polymers / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D012756:Sheep; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D011108:Polymers; D014358:Trypsin Inhibitor, Bowman-Birk Soybean