Reduction in the toxicity of aminopterin--monoclonal-antibody conjugates by leucovorin.
Cancer Immunol Immunother
; 39(2): 135-9, 1994 Aug.
Article
em En
| MEDLINE
| ID: mdl-8044832
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunotoxinas
/
Leucovorina
/
Aminopterina
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cancer Immunol Immunother
Ano de publicação:
1994
Tipo de documento:
Article