Bioaffinity therapy with antibodies and drugs bound to soluble synthetic polymers.
Soluble synthetic copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA) containing different oligopeptide side-sequences were tested as transport molecules for drugs and anti-Thy 1.2 antibodies in affinity therapy. As target cells, T lymphocytes were studied. (1) HPMA copolymers containing targeting anti-Thy 1.2 antibodies are 70 times more cytotoxic against T lymphocytes than HPMA copolymers with non-specific immunoglobulin. (2) Daunomycin conjugated to a biodegradable side-sequence (Gly-Phe-Leu-Gly) is effective in a concentration 100 times lower than daunomycin conjugated to a non-cleavable sequence (Gly-Gly). (3) HPMA copolymers containing drug and targeting antibodies are effective both in vitro and in vivo.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000915:Antibody Affinity; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003630:Daunorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006462:Hemolytic Plaque Technique; D007518:Isoantibodies / Q000008:administration & dosage*; D008689:Methacrylates / Q000138:chemical synthesis; D051379:Mice; D008805:Mice, Inbred A; D011108:Polymers; D051381:Rats
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007518:Isoantibodies; D008689:Methacrylates; D011108:Polymers; C035678:anti-Thy antibody; C029639:2-hydroxypropyl methacrylate; D003630:Daunorubicin