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|Title:||Reduction in the toxicity of aminopterin--monoclonal-antibody conjugates by leucovorin.|
|Authors:||Rowland, A J;Pietersz, Geoffrey A|
|Affiliation:||Austin Research Institute, Austin Hospital, Heidelberg, Vic, Australia.|
|Citation:||Cancer Immunology, Immunotherapy : Cii; 39(2): 135-9|
|Abstract:||Although aminopterin(AMN)-antibody drug conjugates have been demonstrated to have a greatly increased antitumor efficacy compared to the free drug, their use is limited by an increase in systemic toxicity manifested by weight loss and bone marrow suppression. Using a murine thymoma model (E3) in inbred mice, the toxicity of a sublethal dose of free AMN could be prevented by the administration of leucovorin 24 h following drug treatment, whilst maintaining the antitumour effect of the drug. The same rescue protocol completely abrogated the antitumour efficacy of AMN-antibody, although toxicity was also diminished. However, the later administration of leucovorin 48-72 h following a sublethal dose of AMN-antibody conjugates resulted in a maintenance of the anti-tumour efficacy of the immunoconjugates and a reduction in toxicity, with a mean percentage change in mouse weight not significantly different from that of the controls. These studies demonstrate that reversal of toxicity caused by AMN-antibody conjugates can be achieved by leucovorin while maintaining a powerful antitumour effect provided that the dose of leucovorin is administered 48-72 h after the conjugate.|
|Internal ID Number:||8044832|
Mice, Inbred BALB C
Mice, Inbred C57BL
Thymus Neoplasms.drug therapy
|Appears in Collections:||Journal articles|
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