An anti-doxorubicin monoclonal antibody modulates kinetic and dynamic characteristics of the drug.
A monoclonal antibody (MAb) directed against doxorubicin (DXR), denominated MAD II, was found to exert an antidotal action by modulating the kinetic and dynamic characteristics of the drug. In vitro, MAD II has been found to reduce the cytotoxicity of DXR and the drug uptake on spleen lymphocytes more efficiently than on tumor cells (P388 leukemia cells). In vivo, the anti-DXR MAb modified the drug distribution; the drug uptake was found to be reduced in the intestine and myocardial tissues and increased in the tumor, liver and spleen. In mice treated with DXR, the administration of anti-DXR MAb exerted an antidotal activity which was proved by the reduction in body-weight loss and mortality. In contrast, the therapeutic efficacy of the drug in P388-tumor-bearing mice was not influenced by the anti-DXR MAb.
Sardini
A
A
Division of Experimental Oncology E, Istituto Nazionale Tumori, Milan, Italy.
Villa
E
E
Morelli
D
D
Ghione
M
M
Ménard
S
S
Colnaghi
M I
MI
Balsari
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000970:Antineoplastic Agents / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000276:immunology / Q000493:pharmacokinetics* / Q000633:toxicity; D007941:Leukemia P388; D051379:Mice; D008815:Mice, Inbred Strains; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004317:Doxorubicin