Boehringer Mannheim Gmbh

Cancerforskningsfondet Af 1989

Cancerforskningsfonden Af 1989

Cancerforskiningsfonden Af 1989

Keld Dano Slashed

Vincent Ellis

Charles Pyke

Michael Ploug

Niels Behrendt

Ebbe Ro Slashednne

Ettore Appella

Ulrich Kohnert

Ulrich Weidle

Wolf-Dieter Schleuning

Ilse Bartke

Bernhard Konig

Eeva-Marjatta Salonen

Francesco Blasi

Maria Teresa Masucci

Nils Bruenner

Hannele Tapiovaara

Maria Vittoria Cubellis

Peter Kristensen

Ross W Stephens

Ann Louring Roldan

Antti Vaheri

Gunilla Ho slashedyer-Hansen

Ulrich Pessara

Laszlo Patthy

Leif Ro Lund

Lisbeth Birk Mo Slashedller

Jari Pollanen

A monoclonal or polyclonal antibody directed against urokinase plasminogen activator receptor (u-PAR), or a subsequence, analogue or glycosylation variant thereof. Antibodies are disclosed which react with free u-PAR or with complexes between u-PA and u-PAR and which are capable of 1) catching u-PAR in ELISA, or 2) detecting u-PAR, e.g. in blotting, or 3) in radioimmunoprecipitation assay precipitate purified u-PAR in intact or fragment form, or 4) is useful for immunohistochemical detection of u-PAR, e.g. in immunostaining of cancer cells, such as in tissue sections at the invasive front, or 5) inhibits the binding of pro-u-PA and active u-PA and thereby inhibits cell surface plasminogen activation. Methods are disclosed 1) for detecting or quantifying u-PAR, 2) for targeting a diagnostic to a cell containing a u-PAR on the surface, 3) for preventing or counteracting proteolytic activity in a mammal. Methods for for selecting a substance suitable for inhibiting u-PA/u-PAR interaction, for preventing or counteracting localized proteolytical activity in a mammal, for inhibiting the invasion and/or metastasis comprise the use of the antibodies and of nude mice inoculated with human cancer cells which are known to invade and/or metastasize in mice and having a distinct color, f.x. obtained by means of an enzyme and a chromogenic substrate for the enzyme, the color being different from the cells of the mouse.

Antibodies and their use

The invention relates to an antibody which inhibits the binding between u-PA and u-PAR to an extent of at least 90% in an assay as defined in the specification, or an active fragment or immunological equivalent of said antibody. Examples of such antibodies are deposited Jul. 7, 1994 at Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSM) with accession numbers DSM ACC2178 and DSM ACC2179 under the terms and conditions of the Budapest Treaty. The invention furthermore relates to a method for detecting or quantifying u-PAR or a glycosylation variant of u-PAR in a sample by use of an antibody according to the invention. Furthermore, the invention relates to a method for the manufacture of a therapeutic agent for preventing or counteracting localized proteolytic activity using of an antibody of the invention as well as to use of an antibody according to the invention for the preparation of a diagnostic agent which is capable of targeting a diagnostic to a cell that contains a u-PAR on the surface.

Hydrophobic u-PAR binding site

Activation of plasminogen to plasma is inhibited by preventing the binding of a receptor binding form of urokinase-type plasminogen activator to a urokinase-type plasminogen activator receptor in a mammal, thereby preventing the urokinase-type plasminogen activator from converting plasminogen into plasmin. DNA fragments which encode for soluble, active fragments of the urokinase-type plasminogen activator are provided.

Vectors and methods for recombinant production of uPA-binding fragments

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Charlottenlund, Denmark

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