Synergistic tumor treatment with extended-PK IL-2 and therapeutic agents
The present invention relates to methods of treating cancer with a combination of extended-PK IL-2 and one or more therapeutic agents, such as a therapeutic antibody. The methods of the invention are applicable across any type of cancer.
1. A method for treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of a fusion protein consisting of a human IL-2 moiety, an Fc domain and, optionally, a linker; and an effective amount of a therapeutic antibody.
2. The method of claim 1 , wherein the Fc domain is mutated to reduce binding to Fcγ receptors, complement proteins, or both.
3. The method of claim 1 , wherein the fusion protein comprises a monomer of one IL-2 moiety linked to an Fc domain as a heterodimer.
4. The method of claim 1 , wherein the fusion protein comprises a dimer of two IL-2 moieties linked to an Fc domain as a heterodimer.
5. The method of claim 1 , wherein the IL-2 is mutated such that it has higher affinity for the IL-2R alpha receptor compared to unmodified IL-2.
6. The method of claim 1 , wherein the fusion protein and the therapeutic antibody are administered simultaneously or sequentially.
7. The method of claim 1 , wherein the cancer is selected from the group consisting of melanoma, colon cancer, breast cancer, renal cancer, testicular cancer, ovarian cancer, prostate cancer, cancer of the small intestine, cancer of the esophagus, cervical cancer, lung cancer, lymphoma, and leukemia.
8. The method of claim 1 , further comprising administering an additional therapeutic agent selected from the group consisting of a cytokine, and a chemotherapeutic agent.
9. A method of inhibiting growth and/or proliferation of tumor cells in a subject comprising administering an effective amount of a fusion protein consisting of a human IL-2 moiety, an Fc domain and, optionally, a linker; and an effective amount of a therapeutic antibody.
10. A method of increasing recruitment of lymphocytes to the periphery of a tumor in a subject comprising administering an effective amount of a fusion protein consisting of a human IL-2 moiety, an Fc domain and, optionally, a linker; and an effective amount of a therapeutic antibody.
11. A method of stimulating T cells and/or NK cells in a subject comprising administering an effective amount of a fusion protein consisting of a human IL-2 moiety, an Fc domain and, optionally, a linker; and an effective amount of a therapeutic antibody.
12. The method of claim 1 , wherein the fusion protein and the therapeutic antibody are formulated as separate compositions.
13. The method of claim 1 , wherein the therapeutic antibody is selected from the group consisting of trastuzumab, bevacizumab, rituximab, pertuzumab, cetuximab, IMC-1C11, tositumomab, EMD 7200, SGN-30, SGN-15, SGN-33, SGN-40, SGN-35, SGN-70, SGN-75, SGN-17/19, brentuximab vedotin, ipilimumab, ofatumumab, panitumumab, alemtuxumab, gemtuzumab ozogamicin, tremelimumab and daclizumab.
14. The method of claim 9 wherein the Fc domain is mutated to reduce binding to Fcγ receptors, complement proteins, or both.
15. The method of claim 9 , wherein the fusion protein comprises a monomer of one IL-2 moiety linked to an Fc domain as a heterodimer.
16. The method of claim 9 , wherein the fusion protein comprises a dimer of two IL-2 moieties linked to an Fc domain as a heterodimer.
17. The method of claim 9 , wherein the IL-2 is mutated such that it has higher affinity for the IL-2R alpha receptor compared to unmodified IL-2.
18. The method of claim 9 , wherein the fusion protein- and the therapeutic antibody are administered simultaneously or sequentially.
19. The method of claim 9 , wherein the fusion protein and the therapeutic antibody are formulated as separate compositions.
20. The method of claim 9 , further comprising administering an additional therapeutic agent selected from the group consisting of a cytokine, and a chemotherapeutic agent.
21. The method of claim 9 , wherein the therapeutic antibody is selected from the group consisting of trastuzumab, bevacizumab, rituximab, pertuzumab, cetuximab, IMC-1C11, tositumomab, EMD 7200, SGN-30, SGN-15, SGN-33, SGN-40, SGN-35, SGN-70, SGN-75, SGN-17/19, brentuximab vedotin, ipilimumab, ofatumumab, panitumumab, alemtuxumab, gemtuzumab ozogamicin, tremelimumab and daclizumab.
22. The method of claim 10 wherein the Fc domain is mutated to reduce binding to Fcγ receptors, complement proteins, or both.
23. The method of claim 10 , wherein the fusion protein comprises a monomer of one IL-2 moiety linked to an Fc domain as a heterodimer.
24. The method of claim 10 , wherein the fusion protein comprises a dimer of two IL-2 moieties linked to an Fc domain as a heterodimer.
25. The method of claim 10 , wherein the IL-2 is mutated such that it has higher affinity for the IL-2R alpha receptor compared to unmodified IL-2.
26. The method of claim 10 , wherein the fusion protein- and the therapeutic antibody are administered simultaneously or sequentially.
27. The method of claim 10 , wherein the fusion protein and the therapeutic antibody are formulated as separate compositions.
28. The method of claim 10 , further comprising administering an additional therapeutic agent selected from the group consisting of a cytokine, and a chemotherapeutic agent.
29. The method of claim 10 , wherein the therapeutic antibody is selected from the group consisting of trastuzumab, bevacizumab, rituximab, pertuzumab, cetuximab, IMC-1C11, tositumomab, EMD 7200, SGN-30, SGN-15, SGN-33, SGN-40, SGN-35, SGN-70, SGN-75, SGN-17/19, brentuximab vedotin, ipilimumab, ofatumumab, panitumumab, alemtuxumab, gemtuzumab ozogamicin, tremelimumab and daclizumab.
30. The method of claim 11 wherein the Fc domain is mutated to reduce binding to Fcγ receptors, complement proteins, or both.
31. The method of claim 11 , wherein the fusion protein comprises a monomer of one IL-2 moiety linked to an Fc domain as a heterodimer.
32. The method of claim 11 , wherein the fusion protein comprises a dimer of two IL-2 moieties linked to an Fc domain as a heterodimer.
33. The method of claim 11 , wherein the IL-2 is mutated such that it has higher affinity for the IL-2R alpha receptor compared to unmodified IL-2.
34. The method of claim 11 , wherein the fusion protein- and the therapeutic antibody are administered simultaneously or sequentially.
35. The method of claim 11 , wherein the fusion protein and the therapeutic antibody are formulated as separate compositions.
36. The method of claim 11 , further comprising administering an additional therapeutic agent selected from the group consisting of a cytokine, and a chemotherapeutic agent.
37. The method of claim 11 , wherein the therapeutic antibody is selected from the group consisting of trastuzumab, bevacizumab, rituximab, pertuzumab, cetuximab, IMC-1C11, tositumomab, EMD 7200, SGN-30, SGN-15, SGN-33, SGN-40, SGN-35, SGN-70, SGN-75, SGN-17/19, brentuximab vedotin, ipilimumab, ofatumumab, panitumumab, alemtuxumab, gemtuzumab ozogamicin, tremelimumab and daclizumab.
38. The method of claim 1 , wherein the therapeutic antibody binds a cancer antigen.
39. The method of claim 9 , wherein the therapeutic antibody binds a cancer antigen.
40. The method of claim 10 , wherein the therapeutic antibody binds a cancer antigen.
41. The method of claim 11 , wherein the therapeutic antibody binds a cancer antigen.