Treatment of tumorigenic pathophysiological conditions with...

A - Human Necessities – 61 – K

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A61K 47/48 (2006.01) A61K 38/18 (2006.01)

Patent

CA 2089820

Conjugates comprising bFGF or other FGF polypeptides and cytotoxic agent are prepared. The cytotoxic agent can be a ribosome-inactivating protein (RIP), such as saporin, which is attached to bFGF through a chemical bond, or the composition can be prepared as a recombinant DNA chimera. The conjugates are used to specifically target cells, in vivo and in vitro, which express FGF receptors. The cytotoxicity of the conjugates is proportional to the number of receptors expressed by a cell type. The conjugate is useful to effectively treat mammals, and in particular human patients, afflicted with tumorigenic conditions, such as human melanomas, human ovarian carcinomas, teratocarcinomas and neurobiastomas, and other FGF-mediated tumors caused by a proliferation of cells which express FGF receptors.

Conjugués comportant le bFGF ou d'autres polypeptides du FGF et un agent cytotoxique. L'agent cytotoxique peut être une protéine capable d'inactiver le ribosome (RIP), comme la saporine, qui est attachée au bFGF par une liaison chimique ou la composition peut être préparée comme une chimère d'ADN recombinant. Les conjugués sont utilisés pour cibler spécifiquement les cellules, in vivo et in vitro, qui expriment des récepteurs de FGF. La cytotoxicité des conjugués est proportionnelle au nombre de récepteurs exprimés par un type de cellules. Le conjugué est utile dans le traitement des mammifères, en particulier les patients humains, présentant des tumeurs, comme des mélanomes humains, des cancers de l'ovaire humains, des tératocarcinomes et des neuroblastomes et d'autres tumeurs dépendantes du FGF causées par une prolifération des cellules qui expriment des récepteurs du FGF.

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