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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.
Issue Date: 1-Aug-1994
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
Type: Journal Article
Subjects: Aminopterin.toxicity
Antibodies, Monoclonal
Antigens, Ly.immunology
Immunotoxins.analysis.therapeutic use
Leucovorin.therapeutic use
Mice, Inbred BALB C
Mice, Inbred C57BL
Neoplasm Transplantation
Thymoma.drug therapy
Thymus Neoplasms.drug therapy
Appears in Collections:Journal articles

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