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