Fusion molecules of CTLA4 and IL-15
Soluble fusion protein complexes, including domains from IL-15, IL-15 receptor, and αCTLA4 antibody for preventing, reducing the occurrence of, and/or treating cancer or an autoimmune disease or disorder in a subject are provided herein. The methods provided herein include administering to a subject a pharmaceutical composition of a soluble fusion protein complex.
1. A soluble fusion protein complex comprising:
(a): a first domain comprising an interleukin-15 (IL-15) peptide wherein the IL-15 peptide comprises SEQ ID NO: 17 or SEQ ID NO: 1;
(b) a second domain comprising a fusion polypeptide comprising an IL-15 receptor alpha Sushi (IL15RαSu) peptide and an αCTLA4 antibody heavy chain, wherein the αCTLA4 antibody heavy chain has the amino acid sequence of SEQ ID NO: 10; and
(c) a third domain comprising an αCTLA4 antibody light chain having the amino acid sequence of SEQ ID NO: 3;
wherein the IL-15 peptide of the first domain binds to the IL-15RαSu peptide of the second domain to form a soluble fusion protein complex.
2. The soluble fusion protein complex according to claim 1 , wherein the IL-15 peptide comprises SEQ ID NO: 17.
3. The soluble fusion protein complex according to claim 1 , wherein the IL-15 peptide comprises SEQ ID NO: 1.
4. The soluble fusion protein complex according to claim 1 , wherein the fusion polypeptide further comprises a peptide linker between an amino terminus of the IL15RαSu peptide and a carboxy terminus of the αCTLA4 antibody heavy chain.
5. The soluble fusion protein complex according to claim 1 , wherein the fusion polypeptide comprises SEQ ID NO: 5.
6. The soluble fusion protein complex according to claim 1 , wherein the fusion polypeptide further comprises a peptide linker between a carboxy terminus of the IL15RαSu peptide and an amino terminus of the αCTLA4 antibody heavy chain.
7. The soluble fusion protein complex according to claim 6 , wherein the fusion polypeptide comprises SEQ ID NO: 4.
8. A pharmaceutical composition comprising the soluble fusion protein complex according to claim 1 and a pharmaceutically acceptable carrier.
9. The pharmaceutical composition according to claim 8 , wherein the pharmaceutical composition is formulated for parenteral injection.
10. The pharmaceutical composition according to claim 9 , wherein the pharmaceutical composition is formulated for subcutaneous, intravenous, intramuscular, intravesicular, intratumoral or intraperitoneal injection.
11. The pharmaceutical composition according to claim 10 , wherein the composition is formulated for intravenous injection.
12. A method of treating melanoma in a subject in need thereof, the method comprising administering to the subject the soluble fusion protein complex according to claim 1 .