CONSTRUCTION AND CHEMOTHERAPEUTIC POTENTIAL OF CARBOXYPEPTIDASE-A MONOCLONAL-ANTIBODY CONJUGATE

被引：21

作者：

ESSWEIN, A ^{[1
]}

HANSELER, E ^{[1
]}

MONTEJANO, Y ^{[1
]}

VITOLS, KS ^{[1
]}

HUENNEKENS, FM ^{[1
]}

机构：

[1] SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, DIV BIOCHEM, RES INST, LA JOLLA, CA 92037 USA

来源：

ADVANCES IN ENZYME REGULATION | 1991年 / 31卷

关键词：

D O I：

10.1016/0065-2571(91)90005-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Carboxypeptidase-A and a monoclonal antibody (KS1/4) directed against a human lung carcinoma cell line (UCLA-P3) were derivatized by treatment with succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate and N-succinimidyl 3-(2-pyridyldithio)propionate, respectively. Admixture of these entities produced a stable conjugate containing 4 to 5 enzyme molecules per molecule of antibody. The conjugate (Mr ≅ 300 kDa) was purified to homogeneity by HPLC gel filtration and HPLC ion-exchange chromatography. Neither the catalytic activity of the enzyme nor the antigen-binding capacity of the monoclonal antibody was impaired in the conjugate. UCLA-P3 cells that had been exposed to the conjugate and then washed thoroughly were extremely sensitive to methotrexate α-alanine (MTX-Ala), a prodrug form of MTX. At 10-5 m, MTX-Ala was almost as effective as free MTX in blocking the replication of conjugate-treated cells. These results demonstrate the chemotherapeutic potential of enzyme-monoclonal antibody conjugates used in conjunction with prodrugs. © 1991.

引用

页码：3 / +

页数：1

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