Membrane estrogen receptor-directed therapy in breast cancer

A - Human Necessities – 61 – K

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A61K 39/395 (2006.01) A61K 39/40 (2006.01) A61K 39/42 (2006.01) A61K 47/48 (2006.01) C07K 16/28 (2006.01) C07K 16/32 (2006.01) C12N 15/11 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2400874

Methods of diagnosing and treating mammalian tumors with molecules including anti-estrogen receptor immunoglobulin polypeptides are provided. In an illustrative embodiment, anti-estrogen receptor immunoglobulin polypeptides specific to distinct epitopes of the ligand-binding domain of estrogen receptor are contacted with membrane-associated estrogen receptor under conditions which allow binding of the anti-estrogen receptor immunoglobulin polypeptide to a degree sufficient to inhibit tumor growth by inhibiting the activation of the membrane-associated estrogen receptor. Injectable compositions for treating certain mammalian tumors with monoclonal antibodies and methods for diagnosing mammalian cancers which express an estrogen receptor associated with the surface membrane of the cells are also disclosed. Further, alternate methods for blocking intracellular signal transduction emanating from the activation of membrane-associated estrogen receptor forms are also presented. These approaches also appear sufficient to inhibit tumor growth.

L'invention concerne des procédés de diagnostic et traitement de tumeurs mammifères, à l'aide de molécules comprenant des polypeptides (immunoglobulines) dirigés contre le récepteur des oestrogènes. Dans un mode de réalisation, l'invention consiste à mettre en contact de tels polypeptides, spécifiques d'épitopes distincts du domaine de liaison du ligand du récepteur des oestrogènes, avec le récepteur membranaire des oestrogènes, dans des conditions permettant au polypeptide dirigé contre le récepteur des oestrogènes, de se lier à ce récepteur à un degré suffisant pour inhiber la croissance tumorale, en inhibant l'activation du récepteur membranaire des oestrogènes. L'invention concerne encore des compositions injectables destinées à traiter certaines tumeurs mammifères à l'aide d'anticorps monoclonaux, ainsi que des procédés de diagnostic de cancers mammifères qui expriment un récepteur d'oestrogènes associé à la membrane de surface des cellules. En outre, l'invention concerne d'autre méthodes de blocage de la transduction du signal intracellulaire émanant de l'activation des formes du récepteur membranaire des oestrogènes. Ces approches semblent suffisantes pour inhiber la croissance tumorale.

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