Immunotoxin therapy of cancer

被引:417
作者
Pastan, Ira [1 ]
Hassan, Raffit [1 ]
FitzGerald, David J. [1 ]
Kreitman, Robert J. [1 ]
机构
[1] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1038/nrc1891
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Rationally designed anticancer agents that target cell-surface antigens or receptors represent a promising approach for treating cancer patients. However, antibodies that bind these targets are often, by themselves, non-cytotoxic. By attaching potent toxins we can dramatically improve the clinical utility of some anti-tumour antibodies. Here we describe the construction and clinical utility of several recombinant immunotoxins; each of which is composed of antibody Fv fragments fused to powerful bacterial toxins. Results from clinical trials indicate that recombinant immunotoxins and similar agents that are designed to combine antibody selectivity with toxin cell-killing potency will be useful additions to cancer therapy.
引用
收藏
页码:559 / 565
页数:7
相关论文
共 71 条
[1]  
Argani P, 2001, CLIN CANCER RES, V7, P3862
[2]   Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome [J].
Baluna, R ;
Rizo, J ;
Gordon, BE ;
Ghetie, V ;
Vitetta, ES .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :3957-3962
[3]   The effect of a monoclonal antibody coupled to ricin A chain-derived peptides on endothelial cells in vitro:: Insights into toxin-mediated vascular damage [J].
Baluna, R ;
Coleman, E ;
Jones, C ;
Ghetie, V ;
Vitetta, ES .
EXPERIMENTAL CELL RESEARCH, 2000, 258 (02) :417-424
[4]   Immunotherapy of Hodgkin's lymphoma [J].
Borchmann, P ;
Schnell, R ;
Engert, A .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2005, 75 :159-165
[5]   Monoclonal antibodies for brain tumour treatment [J].
Boskovitz, A ;
Wikstrand, CJ ;
Kuan, CT ;
Zalutsky, MR ;
Reardon, DA ;
Bigner, DD .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2004, 4 (09) :1453-1471
[6]   A dominant linear B-cell epitope of ricin A-chain is the target of a neutralizing antibody response in Hodgkin's lymphoma patients treated with an anti-CD25 immunotoxin [J].
Castelletti, D ;
Fracasso, G ;
Righetti, S ;
Tridente, G ;
Schnell, R ;
Engert, A ;
Colombatti, M .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2004, 136 (02) :365-372
[7]   Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers [J].
Chang, K ;
Pastan, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (01) :136-140
[8]   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
[9]   Improving antibody affinity by mimicking somatic hypermutation in vitro [J].
Chowdhury, PS ;
Pastan, I .
NATURE BIOTECHNOLOGY, 1999, 17 (06) :568-572
[10]   Isolation of a high-affinity stable single-chain Fv specific for mesothelin from DNA-immunized mice by phage display and construction of a recombinant immunotoxin with anti-tumor activity [J].
Chowdhury, PS ;
Viner, JL ;
Beers, R ;
Pastan, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (02) :669-674