PRODUCTION AND CHARACTERIZATION OF A SET OF MONOCLONAL-ANTIBODIES AGAINST TISSUE-TYPE PLASMINOGEN-ACTIVATOR (T-PA)

被引:13
作者
BOS, R [1 ]
SIEGEL, K [1 ]
OTTER, M [1 ]
NIEUWENHUIZEN, W [1 ]
机构
[1] TNO, IVVO, GAUBIUS LAB, POB 430, 2300 AK LEIDEN, NETHERLANDS
关键词
D O I
10.1016/0268-9499(92)90057-O
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To generate bispecific monoclonal antibodies, reactive to both fibrin and tissue-type plasminogen activator (t-PA), we planned to generate anti-t-PA monoclonal antibodies (mAb) which eliminate negative aspects of t-PA such as the inhibition by plasminogen activator inhibitor-type 1 (PAI-1) and the rapid clearance of t-PA. Here we report on the isolation and characterisation of a set of 13 mAb against t-PA, some of which meet the above requirements. Apart from their potential in the production of bispecific antibodies, these and the other mAb can be useful in structure-function analysis and a variety of other applications. Experiments involving PAI-1 showed that one mAB (12-5-3) reacts only with free t-PA, and prevents the subsequent binding of PAI-1 to mAb-bound t-PA. In vitro studies on the receptor mediated uptake of t-PA by hepatic cells, showed that one mAb (1-3-1) specifically inhibited the association of t-PA with liver endothelial cells. Other tests showed that mAb 7-8-4 and 12-5-3, but not 1-3-1, inhibited in vitro the enzymatic activity of t-PA. On the basis of these and other observations, we conclude that especially mAb 1-3-1, and in vivo possibly 7-8-4 and 12-5-3 may be good candidates for incorporation in bispecific monoclonal antibodies.
引用
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页码:173 / 182
页数:10
相关论文
共 47 条
  • [1] ASTALDI GCB, 1980, J IMMUNOL, V125, P1411
  • [2] TISSUE-TYPE PLASMINOGEN-ACTIVATOR MUTANTS - THEORETICAL AND CLINICAL CONSIDERATIONS
    BANG, NU
    [J]. CIRCULATION, 1989, 79 (06) : 1391 - 1392
  • [3] ANTIBODY-DIRECTED UROKINASE - A SPECIFIC FIBRINOLYTIC AGENT
    BODE, C
    MATSUEDA, GR
    HUI, KY
    HABER, E
    [J]. SCIENCE, 1985, 229 (4715) : 765 - 767
  • [4] Bos E S, 1981, J Immunoassay, V2, P187, DOI 10.1080/15321818108056977
  • [5] BOS R, 1990, CLONE CLIN, P201
  • [6] BOS R, 1990, CLONE CLIN, P167
  • [7] BOUVET JP, 1984, J IMMUNOL METHODS, V66, P299, DOI 10.1016/0022-1759(84)90341-7
  • [8] BRANSCOMB EE, 1990, THROMB HAEMOSTASIS, V64, P260
  • [9] TISSUE-TYPE PLASMINOGEN-ACTIVATOR - A REVIEW OF ITS PHARMACOLOGY AND THERAPEUTIC USE AS A THROMBOLYTIC AGENT
    COLLEN, D
    LIJNEN, HR
    TODD, PA
    GOA, KL
    [J]. DRUGS, 1989, 38 (03) : 346 - 388
  • [10] COLLEN D, 1988, THROMB RES, P3