The applicability of targeting therapy intervention in lymphatic tissue was studied. The effect was measured as the inhibition of anti-sheep red blood cell antibody response expressed in plaque-forming cells. Daunomycin was used as the effective drug and polyclonal and monoclonal anti-Thy 1.2 or anti-Iak antibody served for targeting. Both components were coupled to a soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer with oligopeptidic side sequences which permitted a controlled release of the drug in the target tissue. HPMA copolymer conjugates with side sequences Gly-Phe-Leu-Gly cleavable by lysosomal enzymes decreased in vivo the antibody reaction by 60-85%. A comparable amount of free targeting antibody was without a significant effect. Injection of targeted daunomycin decreased the toxicity of the drug against hematopoietic precursors in bone marrow colony-forming unit-spleen 80 times compared to the same amount of free drug. The in vivo effectiveness of targeted daunomycin was confirmed morphologically. Application of free daunomycin lead to a significant irritation of Kupffer cells in liver while none of the daunomycin-antibody-copolymer conjugate had such an effect.

Institute of Microbiology Czechoslovak Academy of Sciences Prague

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