A RECOMBINANT IMMUNOTOXIN THAT IS ACTIVE ON PROSTATE-CANCER CELLS AND THAT IS COMPOSED OF THE FV REGION OF MONOCLONAL-ANTIBODY PR1 AND A TRUNCATED FORM OF PSEUDOMONAS EXOTOXIN

被引：32

作者：

BRINKMANN, U ^{[1
]}

GALLO, M ^{[1
]}

BRINKMANN, E ^{[1
]}

KUNWAR, S ^{[1
]}

PASTAN, I ^{[1
]}

机构：

[1] NCI,DIV CANC BIOL DIAGNOSIS,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 | 1993年 / 90卷 / 02期

关键词：

SINGLE-CHAIN IMMUNOTOXIN; CHEMOTHERAPY; IMMUNOTHERAPY;

D O I：

10.1073/pnas.90.2.547

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：

Monoclonal antibody PR1 binds to the surface of normal prostate cells and to adenocarcinomas of the prostate. The cDNAs coding for the heavy and light chain variable regions of monoclonal antibody PR1 were cloned by PCR techniques. A recombinant toxin was then constructed that has the heavy chain variable region of monoclonal antibody PR1 connected to the light chain variable region by a flexible peptide linker to create a single-chain Fv; the Fv in turn is fused to a truncated form of Pseudomonas exotoxin. The resulting recombinant immunotoxin PR1(Fv)-PE38KDEL was produced in Escherichia coli and accumulated in inclusion bodies. After denaturation and renaturation, active monomeric molecules with a molecular mass of almost-equal-to 65 kDa were purified to homogeneity. PR1(Fv)-PE38KDEL binds specifically to cells containing the PR1 antigen and is very cytotoxic toward a subset of LNCaP cells that express the PR1 antigen on their surface.

引用

页码：547 / 551

页数：5

共 21 条

[11]

Kabat EA, 1991, SEQUENCES PROTEINS I

[12]

PADMANABHAN R, 1989, J IMMUNOGENET, V16, P91

[13] ANTITUMOR ACTIVITIES OF IMMUNOTOXINS MADE OF MONOCLONAL-ANTIBODY B3 AND VARIOUS FORMS OF PSEUDOMONAS EXOTOXIN [J].

PAI, LH ;

BATRA, JK ;

FITZGERALD, DJ ;

WILLINGHAM, MC ;

PASTAN, I .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (08) :3358-3362

[14]

PARKS DR, 1986, HDB EXPT IMMUNOLOGY

[15]

PASTAN I, 1991, CANCER RES, V51, P3781

[16] RECOMBINANT TOXINS AS NOVEL THERAPEUTIC AGENTS [J].

PASTAN, I ;

CHAUDHARY, V ;

FITZGERALD, DJ .

ANNUAL REVIEW OF BIOCHEMISTRY, 1992, 61 :331-354

[17] MOLECULAR-BASIS OF AN ISOGENEIC ANTI-IDIOTYPIC RESPONSE [J].

SABLITZKY, F ;

RAJEWSKY, K .

EMBO JOURNAL, 1984, 3 (12) :3005-3012

[18]

SEETHARAM S, 1991, J BIOL CHEM, V266, P17376

[19] USE OF BACTERIOPHAGE-T7 RNA-POLYMERASE TO DIRECT SELECTIVE HIGH-LEVEL EXPRESSION OF CLONED GENES [J].

STUDIER, FW ;

MOFFATT, BA .

JOURNAL OF MOLECULAR BIOLOGY, 1986, 189 (01) :113-130

[20] REDESIGNING NATURES POISONS TO CREATE ANTITUMOR REAGENTS [J].

VITETTA, ES ;

FULTON, RJ ;

MAY, RD ;

TILL, M ;

UHR, JW .

SCIENCE, 1987, 238 (4830) :1098-1104

← 1 2 3 →