AN IL-15 AND IL-15R\alpha SUSHI DOMAIN BASED IMMUNOCYTOKINES

Abstract

The immunocytokine includes (a) a conjugate, and (b) an antibody or a fragment thereof directly or indirectly linked by covalence to the conjugate, wherein the conjugate includes (i) a polypeptide including the amino acid sequence of the interleukin 15 or derivatives thereof, and a polypeptide including the amino acid sequence.

1 . An immunocytokine comprising:
 a) a conjugate, and   b) an antibody or a fragment thereof directly or indirectly linked by covalence to said conjugate,   wherein said conjugate comprises:   (i) a polypeptide comprising the amino acid sequence of the interleukin 15 or derivatives thereof, and   (ii) a polypeptide comprising the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof.   
     
     
         2 . The immunocytokine of  claim 1 , wherein
 a) the polypeptides i) and ii) of the conjugate are covalently linked in a fusion protein; and   b) said conjugate and the antibody or fragment thereof are covalently linked in a fusion protein.   
     
     
         3 . The immunocytokine of  claim 2 , wherein the amino acid sequence of the conjugate and the amino acid sequence of the antibody or fragment thereof are not separated by any linker amino acid sequence. 
     
     
         4 . The immunocytokine of  claim 2 , wherein the amino acid sequence of the conjugate and the amino acid sequence of the antibody or fragment thereof are separated by a second linker amino acid sequence. 
     
     
         5 . The immunocytokine of  claim 1 , wherein said interleukin 15 has the amino acid sequence SEQ ID no 1. 
     
     
         6 . The immunocytokine of  claim 1 , wherein sushi domain of IL-15Rα has the amino acid sequence SEQ ID no 4. 
     
     
         7 . The immunocytokine of  claim 1 , wherein the polypeptide (ii) comprising the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof has the amino acid sequence SEQ ID no 12. 
     
     
         8 . The immunocytokine of  claim 2 , wherein said conjugate comprises the amino acid sequence of the interleukin 15 or derivatives thereof in a C-terminal position relative to the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof. 
     
     
         9 . The immunocytokine of  claim 2 , wherein the amino acid sequence of the interleukin 15 or derivatives thereof and the amino acid sequence of the sushi domain of the IL-15Rα or derivatives are separated by a first linker amino acid sequence. 
     
     
         10 . The immunocytokine of  claim 2 , wherein the antibody or fragment thereof is directed against an antigen selected in the group comprising antigens related to tumor neovascularization or to tumor extracellular matrix and tumoral antigens. 
     
     
         11 . The immunocytokine of  claim 2 , wherein the amino acid sequence of the conjugate is in a C-terminal position relative to the amino acid sequence of the antibody or fragment thereof. 
     
     
         12 . A nucleic acid encoding for an immunocytokine as defined in  claim 1 . 
     
     
         13 . A vector comprising a nucleic acid as defined in  claim 12 . 
     
     
         14 . A host cell genetically engineered with the nucleic acid of  claim 12 , preferably said host cell is an animal cell and most preferably a CHO cell. 
     
     
         15 . A pharmaceutical composition comprising the immunocytokine as defined in  claim 1 , eventually associated with a pharmaceutically acceptable carrier. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein said pharmaceutical composition is for treating cancer in a subject, preferably by an administration by injection at a dose of 2.5 mg/kg of subject or less. 
     
     
         17 . A pharmaceutical composition comprising the nucleic acid of  claim 12 , eventually associated with a pharmaceutically acceptable carrier. 
     
     
         18 . A pharmaceutical composition comprising the vector of  claim 13 , eventually associated with a pharmaceutically acceptable carrier.