Methods of using interleukin-10 for treating diseases and disorders
Methods of treating subjects having diseases, disorders, or conditions, including cancer and immune- and inflammatory-related disorders, via the administration of IL-10 in combination with one or more additional agents, and methods and models associated therewith, are provided.
1. A method of treating cancer in a human, comprising administering to the human:
a) a therapeutically effective amount of an inhibitor of at least one immune checkpoint, wherein the immune checkpoint inhibitor is an anti-PD-1 or anti-PD-L1 antibody, wherein the anti-PD-1 or anti-PD-L1 antibody is selected from the group consisting of nivolumab, lambrolizumab, atezolizumab, and durvalumab; and
b) a therapeutically effective amount of an IL-10 agent, wherein the IL-10 agent is a PEG-IL-10 agent, wherein the IL-10 component of the PEG-IL-10 agent comprises mature human IL-10, and wherein the PEG component of the PEG-IL-10 agent comprises at least one PEG molecule covalently attached to the alpha amino group of the amino acid residue at the N-terminus of IL-10, wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 5 kDa to about 20 kDa, and wherein the amount is sufficient to maintain a mean IL-10 serum trough concentration of at least 1.0 ng/mL; and
wherein the cancer is melanoma, lung cancer, or kidney cancer.
2. The method of claim 1 , wherein the cancer is lung cancer.
3. The method of claim 1 , wherein the cancer is kidney cancer.
4. The method of claim 1 , wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.
5. The method of claim 1 , wherein the administering of the inhibitor of at least one immune checkpoint and the IL-10 agent is by parenteral injection.
6. The method of claim 5 , wherein the administering of the IL-10 agent is by subcutaneous injection.
7. The method of claim 1 , wherein the inhibitor of at least one immune checkpoint and the IL-10 agent are administered simultaneously.
8. The method of claim 1 , wherein the inhibitor of at least one immune checkpoint and the IL-10 agent are administered sequentially.
9. The method of claim 1 , further comprising administering at least one additional prophylactic or therapeutic agent.
10. The method of claim 9 , wherein the prophylactic or therapeutic agent is a chemotherapeutic agent.
11. A method of treating cancer in a human, comprising administering to the human:
a) a therapeutically effective amount of an inhibitor of at least one immune checkpoint, wherein the immune checkpoint inhibitor is an anti-PD-1 or anti-PD-L1 antibody, wherein the anti-PD-1 or anti-PD-L1 antibody is selected from the group consisting of nivolumab, lambrolizumab, atezolizumab, and durvalumab; and
b) a therapeutically effective amount of an IL-10 agent, wherein the IL-10 agent is a PEG-IL-10 agent, wherein the IL-10 component of the PEG-IL-10 agent comprises mature human IL-10, and wherein the PEG component of the PEG-IL-10 agent comprises at least one PEG molecule covalently attached to the alpha amino group of the amino acid residue at the N-terminus of IL-10, wherein the PEG component of the PEG-IL-10 agent has a molecular mass of about 5 kDa, and wherein the amount is sufficient to maintain a mean IL-10 serum trough concentration of at least 1.0 ng/mL; and
wherein the cancer is melanoma, lung cancer, or kidney cancer.
12. The method of claim 11 , wherein the cancer is lung cancer.
13. The method of claim 11 , wherein the cancer is kidney cancer.
14. The method of claim 11 , wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.
15. The method of claim 11 , wherein the administering of the inhibitor of at least one immune checkpoint and the IL-10 agent is by parenteral injection.
16. The method of claim 15 , wherein the administering of the IL-10 agent is by subcutaneous injection.
17. The method of claim 11 , wherein the inhibitor of at least one immune checkpoint and the IL-10 agent are administered simultaneously.
18. The method of claim 11 , wherein the inhibitor of at least one immune checkpoint and the IL-10 agent are administered sequentially.
19. The method of claim 11 , further comprising administering at least one additional prophylactic or therapeutic agent.
20. The method of claim 19 , wherein the prophylactic or therapeutic agent is a chemotherapeutic agent.