Immunotoxins: The Role of the Toxin

被引:102
作者
Antignani, Antonella [1 ]
FitzGerald, David [1 ]
机构
[1] NCI, Biotherapy Sect, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
immunotoxin; antibody; toxin; cancer; immunotherapy; apoptosis; translocation; ricin; diphtheria; Pseudomonas; PHASE-I TRIAL; BONE-MARROW-TRANSPLANTATION; SINGLE-CHAIN IMMUNOTOXINS; VERSUS-HOST-DISEASE; CELL LUNG-CANCER; DIPHTHERIA-TOXIN; RECOMBINANT IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN; RFB4(DSFV)-PE38 BL22; HEMATOLOGIC MALIGNANCIES;
D O I
10.3390/toxins5081486
中图分类号
TS2 [食品工业];
学科分类号
100403 [营养与食品卫生学];
摘要
Immunotoxins are antibody-toxin bifunctional molecules that rely on intracellular toxin action to kill target cells. Target specificity is determined via the binding attributes of the chosen antibody. Mostly, but not exclusively, immunotoxins are purpose-built to kill cancer cells as part of novel treatment approaches. Other applications for immunotoxins include immune regulation and the treatment of viral or parasitic diseases. Here we discuss the utility of protein toxins, of both bacterial and plant origin, joined to antibodies for targeting cancer cells. Finally, while clinical goals are focused on the development of novel cancer treatments, much has been learned about toxin action and intracellular pathways. Thus toxins are considered both medicines for treating human disease and probes of cellular function.
引用
收藏
页码:1486 / 1502
页数:17
相关论文
共 111 条
[1]
AKIYAMA S, 1985, CANCER RES, V45, P1005
[2]
How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane? [J].
Antignani, Antonella ;
Youle, Richard J. .
CURRENT OPINION IN CELL BIOLOGY, 2006, 18 (06) :685-689
[3]
ELIMINATION OF INFECTIOUS HUMAN-IMMUNODEFICIENCY-VIRUS FROM HUMAN T-CELL CULTURES BY SYNERGISTIC ACTION OF CD4-PSEUDOMONAS EXOTOXIN AND REVERSE-TRANSCRIPTASE INHIBITORS [J].
ASHORN, P ;
MOSS, B ;
WEINSTEIN, JN ;
CHAUDHARY, VK ;
FITZGERALD, DJ ;
PASTAN, I ;
BERGER, EA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (22) :8889-8893
[4]
Specific killing of HIV-infected lymphocytes by a recombinant immunotoxin directed against the HIV-1 envelope glycoprotein [J].
Bera, TK ;
Kennedy, PE ;
Berger, EA ;
Barbas, CF ;
Pastan, I .
MOLECULAR MEDICINE, 1998, 4 (06) :384-391
[5]
Immunotoxin Complementation of HAART to Deplete Persisting HIV-Infected Cell Reservoirs [J].
Berger, Edward A. ;
Pastan, Ira .
PLOS PATHOGENS, 2010, 6 (06)
[6]
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
[7]
IMMUNOTOXINS - HYBRID MOLECULES OF MONOCLONAL-ANTIBODIES AND A TOXIN SUBUNIT SPECIFICALLY KILL TUMOR-CELLS [J].
BLYTHMAN, HE ;
CASELLAS, P ;
GROS, O ;
GROS, P ;
JANSEN, FK ;
PAOLUCCI, F ;
PAU, B ;
VIDAL, H .
NATURE, 1981, 290 (5802) :145-146
[8]
A RECOMBINANT IMMUNOTOXIN CONTAINING A DISULFIDE-STABILIZED FV FRAGMENT [J].
BRINKMANN, U ;
REITER, Y ;
JUNG, SH ;
LEE, B ;
PASTAN, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (16) :7538-7542
[9]
INDEPENDENT DOMAIN FOLDING OF PSEUDOMONAS EXOTOXIN AND SINGLE-CHAIN IMMUNOTOXINS - INFLUENCE OF INTERDOMAIN CONNECTIONS [J].
BRINKMANN, U ;
BUCHNER, J ;
PASTAN, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) :3075-3079
[10]
A METHOD FOR INCREASING THE YIELD OF PROPERLY FOLDED RECOMBINANT FUSION PROTEINS - SINGLE-CHAIN IMMUNOTOXINS FROM RENATURATION OF BACTERIAL INCLUSION-BODIES [J].
BUCHNER, J ;
PASTAN, I ;
BRINKMANN, U .
ANALYTICAL BIOCHEMISTRY, 1992, 205 (02) :263-270