B3(FV)-PE38KDEL, A SINGLE-CHAIN IMMUNOTOXIN THAT CAUSES COMPLETE REGRESSION OF A HUMAN CARCINOMA IN MICE

被引：229

作者：

BRINKMANN, U ^{[1
]}

PAI, LH ^{[1
]}

FITZGERALD, DJ ^{[1
]}

WILLINGHAM, M ^{[1
]}

PASTAN, I ^{[1
]}

机构：

[1] NCI,DIV CANC BIOL,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1991年 / 88卷 / 19期

关键词：

MONOCLONAL ANTIBODY B3; SINGLE-CHAIN ANTIGEN-BINDING PROTEIN; PSEUDOMONAS EXOTOXIN; CANCER THERAPY;

D O I：

10.1073/pnas.88.19.8616

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The genes encoding the heavy- and light-chain Fv regions of the monoclonal murine antibody B3, which recognizes a carbohydrate antigen on the surface of many human carcinomas, were cloned by PCR techniques and used to generate single-chain immunotoxins containing Pseudomonas exotoxin (PE). The light and heavy chains were connected by a flexible linker to form a single-chain antigen-binding protein, B3(Fv), which was in turn fused to truncated forms of PE lacking the cell-binding domain. The single-chain Fv and two different B3(Fv) immunotoxins, B3(Fv)-PE40 and B3(Fv)-PE38KDEL, were expressed in Escherichia coli and the single-chain immunotoxins were purified to near homogeneity. Both recombinant immunotoxins were shown to be cytotoxic specifically to carcinoma cell lines that express the B3 antigen on their surface; B3(Fv)-PE38KDEL was significantly more active. Furthermore, intravenous administration of B3(Fv)-PE-38KDEL caused complete regression of human epidermoid carcinomas growing subcutaneously in immunodeficient mice.

引用

页码：8616 / 8620

页数：5

共 23 条

[1] ANTITUMOR-ACTIVITY IN MICE OF AN IMMUNOTOXIN MADE WITH ANTI-TRANSFERRIN RECEPTOR AND A RECOMBINANT FORM OF PSEUDOMONAS EXOTOXIN [J].

BATRA, JK ;

JINNO, Y ;

CHAUDHARY, VK ;

KONDO, T ;

WILLINGHAM, MC ;

FITZGERALD, DJ ;

PASTAN, I .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (21) :8545-8549

[2]

BATRA JK, 1990, J BIOL CHEM, V265, P15198

[3] SINGLE-CHAIN ANTIGEN-BINDING PROTEINS [J].

BIRD, RE ;

HARDMAN, KD ;

JACOBSON, JW ;

JOHNSON, S ;

KAUFMAN, BM ;

LEE, SM ;

LEE, T ;

POPE, SH ;

RIORDAN, GS ;

WHITLOW, M .

SCIENCE, 1988, 242 (4877) :423-426

[4] CONSTRUCTION AND CHARACTERIZATION OF NEW CLONING VEHICLES .2. MULTIPURPOSE CLONING SYSTEM [J].

BOLIVAR, F ;

RODRIGUEZ, RL ;

GREENE, PJ ;

BETLACH, MC ;

HEYNEKER, HL ;

BOYER, HW ;

CROSA, JH ;

FALKOW, S .

GENE, 1977, 2 (02) :95-113

[5] A COMPLEMENTATION ANALYSIS OF RESTRICTION AND MODIFICATION OF DNA IN ESCHERICHIA COLI [J].

BOYER, HW ;

ROULLAND.D .

JOURNAL OF MOLECULAR BIOLOGY, 1969, 41 (03) :459-&

[6]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P848

[7] A RAPID METHOD OF CLONING FUNCTIONAL VARIABLE-REGION ANTIBODY GENES IN ESCHERICHIA-COLI AS SINGLE-CHAIN IMMUNOTOXINS [J].

CHAUDHARY, VK ;

BATRA, JK ;

GALLO, MG ;

WILLINGHAM, MC ;

FITZGERALD, DJ ;

PASTAN, I .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (03) :1066-1070

[8] A RECOMBINANT SINGLE-CHAIN IMMUNOTOXIN COMPOSED OF ANTI-TAC VARIABLE REGIONS AND A TRUNCATED DIPHTHERIA-TOXIN [J].

CHAUDHARY, VK ;

GALLO, MG ;

FITZGERALD, DJ ;

PASTAN, I .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (23) :9491-9494

[9] A RECOMBINANT IMMUNOTOXIN CONSISTING OF 2 ANTIBODY VARIABLE DOMAINS FUSED TO PSEUDOMONAS EXOTOXIN [J].

CHAUDHARY, VK ;

QUEEN, C ;

JUNGHANS, RP ;

WALDMANN, TA ;

FITZGERALD, DJ ;

PASTAN, I .

NATURE, 1989, 339 (6223) :394-397

[10] PSEUDOMONAS EXOTOXIN CONTAINS A SPECIFIC SEQUENCE AT THE CARBOXYL TERMINUS THAT IS REQUIRED FOR CYTOTOXICITY [J].

CHAUDHARY, VK ;

JINNO, Y ;

FITZGERALD, D ;

PASTAN, I .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (01) :308-312

← 1 2 3 →