Homing pro-apoptotic conjugates and methods of using same

Details Homing pro-apoptotic conjugates and methods of using same Homing pro-apoptotic conjugates and methods of using same

A - Human Necessities

61

K

A61K 38/00 (2006.01) A61K 38/04 (2006.01) A61K 39/00 (2006.01) A61K 39/02 (2006.01) A61K 47/48 (2006.01) C07K 2/00 (2006.01) C07K 4/00 (2006.01) C07K 5/00 (2006.01) C07K 7/00 (2006.01) C07K 14/00 (2006.01) C07K 16/00 (2006.01) C07K 17/00 (2006.01)

Patent

CA 2359633

The present invention provides a homing pro-apoptotic conjugate, which includes a tumor homing molecule that selectively homes to a selected mammalian cell type or tissue linked to an antimicrobial peptide, where the conjugate is selectively internalized by the mammalian cell type or tissue and exhibits high toxicity thereto, and where the antimicrobial peptide has low mammalian cell toxicity when not linked to the tumor homing molecule. A homing pro-apoptotic conjugate of the invention can be, for example, CNGRC-GG- D(KLAKLAK)2 or ACDCRGDCFC-GG-D(KLAKLAK)2. The conjugates of the invention are useful, for example, for treating a patient with a tumor having angiogenic vasculature.

La présente invention concerne un conjugué pro-apoptotique de domiciliation renfermant une molécule de ciblage de tumeur qui cible sélectivement un type déterminé de cellule ou de tissu de mammifère lié à un peptide anti-microbien. Ce conjugué est internalisé sélectivement par ce type de cellule ou ce tissu de mammifère, à l'égard duquel il manifeste une toxicité élevée. Le peptide antimicrobien a une faible toxicité à l'égard de la cellule de mammifère lorsqu'il n'est pas lié à la molécule de ciblage de la tumeur. Le conjugué pro-apoptotique selon l'invention peut être, par exemple, CNGRC-GG-¿D?(KLAKLAK)¿2? ou ACDCRGDCFC-GG-¿D?(KLAKLAK)¿2?. Ces conjugués conviennent notamment pour le traitement d'un patient porteur d'une tumeur à vasculature angiogénique.

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