Antibody-targeted polymer-bound drugs.
Drug targeting is an attractive new approach to killing cancer cells while leaving normal tissue unharmed. Recently we have developed a new generation of antibody-targeted immunosuppressive (cyclosporin A) and cytostatic (daunomycin, doxorubicin) drugs and photosensitizers (chlorin e6) effective in vitro and in vivo. The drugs and the targeting antibody (polyclonal and monoclonal) are conjugated to the oligopeptidic side chains of a water-soluble synthetic carrier, copolymer of N-(2-hydroxypropyl)methacrylamide. The composition of the side chains ensures the stability of the linkage between the drug and the polymeric carrier in the bloodstream and its intralysosomal degradability which is a prerequisite for the pharmacological activity of the preparation. Antibody-targeted polymer bound drugs show considerably decreased hepatotoxicity, cardiotoxicity, myelotoxicity and nephrotoxicity. Two adriamycin-HPMA copolymers are in Phase I/II clinical trials in United Kingdom.
Ríhová
B
B
Department of Immunology and Gnotobiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
D000178:Acrylamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002735:Chlorophyllides; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003630:Daunorubicin / Q000627:therapeutic use; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy; D011109:Polymethacrylic Acids / Q000627:therapeutic use; D011166:Porphyrins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018800:Thy-1 Antigens / Q000276:immunology; D014018:Tissue Distribution
D000178:Acrylamides; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002735:Chlorophyllides; D000949:Histocompatibility Antigens Class II; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D011109:Polymethacrylic Acids; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D018800:Thy-1 Antigens; C055174:daunomycin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate; C055176:doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate; C062985:phytochlorin; D004317:Doxorubicin; D016572:Cyclosporine; C032976:N-(2-hydroxypropyl)methacrylamide; D003630:Daunorubicin