Cancerforskningsfondet Af 1989

Cancerforskningsfonden Af 1989

Boehringer Mannheim Gmbh

Cancerforskiningsfonden Af 1989

Vincent Ellis

Charles Pyke

Niels Behrendt

Michael Ploug

Keld Dano Slashed

Ettore Appella

Eeva-Marjatta Salonen

Ann Louring Roldan

Ross W Stephens

Peter Kristensen

Antti Vaheri

Maria Teresa Masucci

Ebbe Ro Slashednne

Hannele Tapiovaara

Francesco Blasi

Maria Vittoria Cubellis

Keld Dan&oslash;

Nils Bruenner

Ulrich Kohnert

Ulrich Weidle

Wolf-Dieter Schleuning

Bernhard Konig

Ilse Bartke

Keld Dano

Gunilla Ho slashedyer-Hansen

Ulrich Pessara

Gunilla Hoyer-Hansen

Ebbe Ronne

Laszlo Patthy

Lisbeth Birk M&oslash;ller

Lisbeth Birk Mo Slashedller

Jari Pollanen

Leif R&oslash;ge Lund

Jari P&ouml;ll&auml;nen

L&aacute;szlo Patthy

Jan Gr&oslash;ndahl-Hansen

John R&oslash;mer

Leif Ro Lund

Helle Pedersen

Ebbe R&oslash;nne

Nils Br&uuml;nner

Wd Schleuning

Heine H&oslash;i Hansen

Activation of plasminogen to plasmin 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 receptor are provided.

Urokinase-type plasminogen activator receptor

The present invention relates to methods for inhibiting malignant tumour growth, invasion and/or metastasis in a patient, the method comprising suppressing the inhibitory activity of an inhibitor of a protease or of a non-proteolytic matrix-degrading enzyme (IPNME) in malignant tumour tissue or potential malignant tumour tissue. The suppression may be brought about by administering compounds interacting with the IPNME, but also administration of compounds interacting with transcription of genes encoding the IPNME is a possibility. The invention also relates to methods of selecting and identifying compounds in the therapeutical methods, as well of the use of such compounds in the treatment of malignancies.

Suppression of inhibitors

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

Urokinase-type plasminogen activator receptor antibodies

Growing community of inventors

Copenhagen, Denmark

Vincent Ellis