IL-15-based molecules and methods of treating a neoplasia

Patent metadata

Field	Value
Publication number	US-12186372-B2
Application number	US-202318176196-A
Country	US
Kind code	B2
Filing date	Feb 28, 2023
Priority date	Jun 30, 2014
Publication date	Jan 7, 2025
Grant date	Jan 7, 2025

Abstract

The invention features combination therapies using an IL-15-based superagonist complex and an antibody to effectively treat subjects with cancer and infectious diseases.

First claim

What is claimed is:

1. A method for treating non-small cell lung carcinoma in a human subject, wherein the subject has been previously treated with an anti-PD-1 or anti-PD-L1 antibody and subsequently experienced disease progression, the method comprising: administering to said subject a pharmaceutical composition comprising an effective amount of an anti-PD-1 or anti-PD-L1 immune checkpoint inhibitor antibody and an effective amount of an IL-15:IL-15RαSu complex, thereby treating the carcinoma.

2. The method of claim 1 , wherein IL-15:IL-15RαSu complex comprises a stabilized IL-15RαSu fusion protein.

3. The method of claim 2 , wherein the stabilized IL-15RαSu fusion protein comprises an immunoglobulin Fc domain.

4. The method of claim 1 , wherein the IL-15:IL-15RαSu complex comprises wild type IL-15.

5. The method of claim 3 , wherein the stabilized IL-15RαSuFc fusion protein comprises the amino acid sequence of SEQ ID NO: 6.

6. The method of claim 1 , wherein the effective amount of said IL-15:IL-15RαSu complex is administered daily.

7. The method of claim 1 wherein the effective amount of said IL-15:IL-15RαSu complex is between 0.1 μg/kg and 100 mg/kg.

8. The method of claim 1 , wherein the effective amount of said IL-15:IL-15RαSu complex is administered once or twice per week.

9. The method of claim 7 , wherein the effective amount of said IL-15:IL-15RαSu complex is between 0.1 μg/kg and 1 mg/kg.

10. The method of claim 1 , wherein the IL-15:IL-15RαSu complex is administered systemically, intravenously, subcutaneously, intramuscularly, intravesically, or by instillation.

11. The method of claim 1 , wherein antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody dependent cellular phagocytosis (ADCP) mediated by said antibody against tumor cells in said subject is induced following said administration.

12. The method of claim 1 , wherein said antibody and said IL-15:IL-15αSu complex increases levels of blood NK cell, T cell, neutrophil or monocyte counts or activity.

13. The method of claim 1 , wherein said antibody and said IL-15:IL-15RαSu complex stimulate CD4+ or CD8+ T cells to kill tumor cells.

14. The method of claim 1 , wherein said antibody and said IL-15:IL-15αSu complex stimulate NK cells to kill tumor cells.

15. The method of claim 1 , wherein said antibody and said IL-15:IL-15RαSu complex stimulate neutrophils or monocytic cells to kill tumor cells.

16. The method of claim 1 , wherein said administration results in a decrease in the number of tumor cells.

17. The method of claim 1 , wherein said administration results in a decrease in disease progression of the carcinoma.

18. The method of claim 1 , wherein said administration results in prolonged survival of said subject compared to an untreated subject.

19. The method of claim 1 , wherein said antibody and said IL-15:IL-15RαSu complex increase blood cytokine levels.

20. The method of claim 19 , wherein said cytokine comprises IFN-γ or IL-6.

21. The method of claim 1 , wherein the antibody and pharmaceutical composition are administered in combination with surgery, radiation therapy, chemotherapy, protein-based therapy and/or biological therapy.

Assignees

• Altor Bioscience Llc

Inventors

• Liu Bai
• Rhode Peter
• Xu Wenxin
• Wong Hing C

Classifications

• C07K2319/32

  fusions with soluble part of a cell surface receptor, "decoy receptors" · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K38/1793

  for cytokines; for lymphokines; for interferons · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title