Regression of established breast carcinoma xenografts with antibody-directed enzyme prodrug therapy against c-erbB2 p185.
Cancer Res
; 54(19): 5171-7, 1994 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-7923136
ABSTRACT
The enzyme carboxypeptidase G2 (CPG2) was conjugated to the rat IgG2a monoclonal antibody (mAb) ICR12, which recognizes the external domain of the human c-erbB2 protooncogene product. The conjugate retained antigen-binding and enzyme activity. Radiolabeled conjugate localized efficiently and stably to MDA MB 361 breast carcinoma xenografts, which overexpress the c-erbB2 gene product p185. Radiotracer determinations and plasma enzyme activity studies in nu/nu mice gave conjugate blood clearance rate half-lives of approximately 4 days. In separate antibody-directed enzyme prodrug therapy regimes, one dose of the 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid prodrug was administered to nu/nu mice bearing established MDA MB 361 tumors (mean volume, 170-260 mm3). In mice which had received ICR12-CPG2 12-14 days previously, sustained dose-dependent tumor stasis or regressions were effected, which in some cases persisted throughout observation periods of up to 90 days. In control mice which had received the isotype-matched irrelevant mAb ICR16-CPG2 conjugate, tumors grew progressively, as did those in mice treated with prodrug alone, or treated simultaneously with ICR12-CPG2 and prodrug at the maximum tolerated dose. Control chemotherapy with conventional drugs proved toxic and induced only minimal growth delays.
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Base de dados:
MEDLINE
Assunto principal:
Pró-Fármacos
/
Gama-Glutamil Hidrolase
/
Receptor ErbB-2
/
Neoplasias Mamárias Experimentais
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Anticorpos Monoclonais
Idioma:
En
Ano de publicação:
1994
Tipo de documento:
Article