PMID- 2891460 OWN - NLM STAT- MEDLINE DCOM- 19880217 LR - 20190820 IS - 0090-1229 (Print) IS - 0090-1229 (Linking) VI - 46 IP - 1 DP - 1988 Jan TI - Antibody-directed affinity therapy applied to the immune system: in vivo effectiveness and limited toxicity of daunomycin conjugated to HPMA copolymers and targeting antibody. PG - 100-14 AB - 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. FAU - Rihova, B AU - Rihova B AD - Institute of Microbiology, Czechoslovak Academy of Sciences, Prague. FAU - Kopeckova, P AU - Kopeckova P FAU - Strohalm, J AU - Strohalm J FAU - Rossmann, P AU - Rossmann P FAU - Vetvicka, V AU - Vetvicka V FAU - Kopecek, J AU - Kopecek J LA - eng PT - Journal Article PL - United States TA - Clin Immunol Immunopathol JT - Clinical immunology and immunopathology JID - 0356637 RN - 0 (Acrylates) RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, Surface) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Methacrylates) RN - 0 (Thy-1 Antigens) RN - UKW89XAX2X (hydroxypropyl methacrylate) RN - ZS7284E0ZP (Daunorubicin) SB - IM MH - Acrylates/*administration & dosage MH - Animals MH - Antibodies, Monoclonal/*administration & dosage MH - Antigens, Surface/immunology MH - Colony-Forming Units Assay MH - Daunorubicin/administration & dosage/*pharmacokinetics/toxicity MH - Female MH - Hematopoietic Stem Cells/drug effects MH - Histocompatibility Antigens Class II/immunology MH - Methacrylates/*administration & dosage MH - Mice MH - Mice, Inbred A MH - Spleen/cytology MH - Thy-1 Antigens MH - Tissue Distribution EDAT- 1988/01/01 00:00 MHDA- 1988/01/01 00:01 CRDT- 1988/01/01 00:00 PHST- 1988/01/01 00:00 [pubmed] PHST- 1988/01/01 00:01 [medline] PHST- 1988/01/01 00:00 [entrez] AID - 10.1016/0090-1229(88)90010-4 [doi] PST - ppublish SO - Clin Immunol Immunopathol. 1988 Jan;46(1):100-14. doi: 10.1016/0090-1229(88)90010-4.