Sirna against cbl-b and optionally il-2 and il-12 for use in the treatment of cancer

Abstract

The invention relates to a method for the immune activation of NK cells by the reduction or inhibition of the Cbl-b function in said cells. This stimulates the congenital immune system and thus permits the therapy of appropriate diseases.

What is claimed is: 
     
         1 . A method of treating cancer in a patient comprising administering at least one Cbl-b inhibitory nucleic acid further defined as an antisense oligonucleotide, siRNA, or shRNA, in combination with at least one NK cell-stimulatory substance further defined as IL-2, IFN-alpha, IL-12 and IL-7, or IL-12 and IL-15 to at least one NK cell of the patient in vivo and/or ex vivo, thereby immune activating the at least one NK cell. 
     
     
         2 . The method of  claim 1 , wherein when the Cbl-b inhibitor is administered in combination with IL-2, one or more of IL-12, IL-23, IFN-alpha, or IFN-beta, or any combination thereof is also administered. 
     
     
         3 . The method of  claim 1 , wherein when the Cbl-b inhibitor is administered in combination with IFN-alpha, one or both of IL-15 or IL-21 is also administered. 
     
     
         4 . The method of  claim 1 , wherein when the Cbl-b inhibitor is administered in combination with IL-12, one or both of IL-15 or IL-7 is also administered. 
     
     
         5 . The method of  claim 1 , wherein the Cbl-b inhibitor and at least one further NK cell-stimulatory substance is administered in combination with at least one of an immune cell-stimulatory cytokine, an interferon or interferon stimulator, an antibody having an Fc domain, or a TLR or PAMP receptor ligand. 
     
     
         6 . The method of  claim 1 , wherein the Cbl-b inhibitor and at least one further NK cell-stimulatory substance is administered in combination with at least one of a cytokine of the common gamma-chain cytokine, a cytokine of both the adaptive and the innate immune system, an effector cell cytokine, a TLR receptor agonist, or a PAMP receptor agonist. 
     
     
         7 . The method of  claim 1 , wherein the at least one Cbl-b inhibitor and the at least one further NK cell-stimulatory substance are comprised in one or more pharmaceutically acceptable carrier. 
     
     
         8 . The method of  claim 7 , wherein the pharmaceutically acceptable carrier is suitable for intracellular administration in a patient. 
     
     
         9 . The method of  claim 8 , wherein the pharmaceutically acceptable carrier is a liposomal or microsomal formulation. 
     
     
         10 . The method of  claim 1 , wherein the patient is a mammal. 
     
     
         11 . The method of  claim 10 , wherein the patient is a human.