Methods of treating a neoplasia with IL-15-based molecules and CTLA-4 antibody

Patent metadata

Field	Value
Publication number	US-12097244-B2
Application number	US-202318394409-A
Country	US
Kind code	B2
Filing date	Dec 22, 2023
Priority date	Jun 30, 2014
Publication date	Sep 24, 2024
Grant date	Sep 24, 2024

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 a CTLA-4 ligand expressing neoplasia in a subject, the method comprising: administering to said subject a pharmaceutical composition comprising an effective amount of an isolated anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody and an effective amount of an IL-15:IL-15RαSu complex, wherein the effective amount of the IL-15:IL-15RαSu complex is between 0.1 μg/kg and 100 mg/kg, thereby treating the neoplasia.

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

3. The method of claim 1 , wherein the IL-15:IL-15RαSu complex comprises an IL-15 molecule having the amino acid sequence of SEQ ID NO:3.

4. The method of claim 1 , wherein the IL-15:IL-15RαSu complex comprises an IL-15RαSuFc fusion construct, having the amino acid sequence of SEQ ID NO:6.

5. The method of claim 1 , wherein the IL-15:IL-15RαSu complex is Alt-803.

6. The method of claim 1 , wherein the subject is suffering from a CTLA-4 ligand expressing neoplasia and the neoplasia is selected from the group consisting of a glioblastoma, prostate cancer, multiple myeloma, B-cell lymphoma, Hodgkin's lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, cutaneous T-cell lymphoma, T-cell lymphoma, urothelial carcinoma, bladder carcinoma, melanoma, lung cancer, renal cell carcinoma, breast cancer, gastric cancer, esophageal cancer, head and neck cancer, colorectal cancer, ovarian cancer, non-small cell lung carcinoma (NSCLC), B-Cell non-Hodgkin's lymphoma, and squamous cell head and neck carcinoma.

7. The method of claim 6 , wherein the subject is suffering from melanoma, renal cell carcinoma, or NSCLC.

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

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

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

11. The method of claim 1 , wherein the pharmaceutical composition is administered by subcutaneous, intravenous, intraperitoneal, intramuscular, or intradermal injection, or by intravesicular instillation.

12. The method of claim 1 , wherein the anti-CTLA-4 antibody is ipilimumab, ticilimumab, tremelimumab.

13. 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.

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

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

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

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

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

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

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

21. The method of claim 1 , wherein said subject is a human.

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

23. The method of claim 22 , wherein said cytokine is interferon-gamma (IFN-γ) or interleukin-6 (IL-6).

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