In vitro and in vivo prodrug therapy of prostate cancer using anti-gamma-Sm-scFv/hCPA fusion protein.
Prostate
; 66(8): 858-66, 2006 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-16491483
ABSTRACT
BACKGROUND:
Raising selectivity to tumor cells is a major challenge for most chemotherapy drugs. One of approaches to realizing this goal is antibody-directed enzyme prodrug therapy (ADEPT). This study was done to investigate the curative effect of a new ADEPT system for the treatment of prostate cancer.METHODS:
Methotrexate (MTX) prodrugs were synthesized and anti-seminoprotein (SM) single-chain antibody/human carboxypeptidase-A fusion protein (scFv/hCPA) was prepared. Therapeutic effects of this ADEPT system were evaluated.RESULTS:
The synthesis of prodrugs was successful and the prodrugs were confirmed no cytotoxicity, but hydrolysis with tumor-targeted scFv/hCPA fusion protein gave 1,000-fold higher cytotoxicity than MTX-alpha-Phe only. Cell cycle assays showed that tumor cells were arrested in the S phase after ADEPT treatment; furthermore, tumors were inhibited significantly in scFv/hCPA and MTX-alpha-Phe treated mice.CONCLUSIONS:
Our results suggest that targeted activation cytotoxicity against established prostate cancer by scFv/hCPA mediated ADEPT is tumor-specific and has no systemic toxicity in vitro and in vivo.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenilalanina
/
Neoplasias de la Próstata
/
Proteínas Recombinantes de Fusión
/
Profármacos
/
Metotrexato
/
Sistemas de Liberación de Medicamentos
/
Carboxipeptidasas A
Idioma:
En
Revista:
Prostate
Año:
2006
Tipo del documento:
Article
País de afiliación:
China