Marked therapeutic efficacy of a novel polyethylene glycol-SN38 conjugate, EZN-2208, in xenograft models of B-cell non-Hodgkin's lymphoma.
Haematologica
; 94(10): 1456-9, 2009 Oct.
Article
em En
| MEDLINE
| ID: mdl-19794091
ABSTRACT
Examination of the clinical utility of SN38 (10-hydroxy-7-ethyl-camptothecin), the active metabolite of CPT-11, has not been possible to date due to poor solubility of SN38. Here we evaluated the activity of EZN-2208, a water-soluble polyethyleneglycol-SN38 conjugate, in pre-clinical models of Burkitt's non-Hodgkin's lymphoma (NHL) (Raji and Daudi), and follicular NHL (DoHH2). In vitro, the IC50 of EZN-2208 ranged from 3-24 nM, which was 30- to 45-fold lower than CPT-11 or 2.5- to 3.5-fold higher than SN38. In both an early-disease Raji model and an advanced-disease Daudi model, treatment with multiple doses of EZN-2208 resulted in 90% and 100% cures of animals, respectively (cure defined as no sign of tumors by gross observations at the termination of study). The activity of EZN-2208 was dramatically superior to that of CPT-11 in all three models. The excellent therapeutic efficacy of EZN-2208 in several B-cell NHL xenograft models merits its evaluation in the clinic for lymphoid malignancies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
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Camptotecina
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Linfoma de Células B
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Ensaios Antitumorais Modelo de Xenoenxerto
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Haematologica
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos