JPWO2020186053A5 - - Google Patents

Claims (34)

A method of converting a non-responder to an anti-PD-L1 or anti-PD-1 cancer therapy into a responder, the method comprising: treating said non-responder in combination with said anti-PD-L1 or anti-PD-1 cancer therapy; A method comprising administering a synergistically therapeutically effective amount of an anti-RGMb antibody. 2. The method of claim 1, wherein the non-responder exhibits resistance to the anti-PD-L1 or anti-PD-1 cancer therapy due to or suspected of being due to dysbiosis. The dysbiosis is caused by one or more conditions selected from intestinal infections, ulcerative colitis, Crohn's disease, irritable bowel syndrome, colon cancer, significant changes in diet, and combinations thereof. , the method according to claim 2. Any one of claims 1 to 3, wherein the non-responder has one or more symptoms selected from diarrhea, constipation, abdominal cramps, loose stools, abnormal amounts of gas or bloating, and combinations thereof. The method described in. 5. The method of any one of claims 1-4, wherein at least one antibiotic is administered to the non-responder within a period of time prior to the anti-PD-L1 or anti-PD-1 cancer therapy. 6. The method of claim 5, wherein the at least one antibiotic is vancomycin, neomycin, metronidazole, ampicillin or a combination thereof. 7. A method according to claim 5 or 6, wherein the certain period of time is at least one week. 8. The non-responder's gastrointestinal microbiota comprises elevated levels of E. coli or bacteria other than Bacteroidetes and Firmicutes compared to cancer-free subjects. Method. 9. The method of any one of claims 1-8, wherein said anti-RGMb antibody is administered for at least one week. The anti-RGMb antibody may be administered intraperitoneally, subcutaneously, intramuscularly, intravenously, intrathecally, intracerebrally, orally, nasally, rectally, intravaginally, parenterally, intracisternally, topically, orally or 10. The method according to any one of claims 1 to 9, wherein the method is administered sublingually. A method according to any one of claims 1 to 10, wherein the cancer therapy is for the treatment of cancer, including solid tumors. A method according to any one of claims 1 to 11, wherein the cancer therapy is for the treatment of adenocarcinoma or colorectal tumors. 13. The method of any one of claims 1-12, wherein administration of an anti-RGMb antibody in combination with anti-PD-1 or anti-PD-L1 cancer therapy results in a synergistic reduction in tumor volume. 14. The method of any one of claims 1-13, wherein the non-responder is a non-responder to anti-PD-1 cancer therapy. 15. The method of any one of claims 1-14, wherein the non-responder is a non-responder to anti-PD-L1 cancer therapy. Use of anti-PD-L1 or anti-PD-1 cancer therapy in combination with an anti-RGMb antibody in the manufacture of a medicament for treating or preventing cancer in a subject, the use of anti-PD-L1 or anti-PD-1 cancer therapy in the manufacture of a medicament for treating or preventing cancer in a subject, Refractory to PD-1 cancer therapy, use. 17. The use according to claim 16, wherein the anti-RGMb antibody administered in combination with the anti-PD-L1 or anti-PD-1 cancer therapy results in a synergistic reduction in tumor volume. A method of converting a non-responder to an anti-PD-L1 or anti-PD-1 cancer therapy into a responder, the method comprising: treating said non-responder in combination with said anti-PD-L1 or anti-PD-1 cancer therapy; A method comprising administering a synergistically therapeutically effective amount of an anti-PD-L2 antibody. 19. The method of claim 18, wherein the non-responder exhibits resistance to the anti-PD-L1 or anti-PD-1 cancer therapy due to or suspected of being due to dysbiosis. The dysbiosis is caused by one or more conditions selected from intestinal infections, ulcerative colitis, Crohn's disease, irritable bowel syndrome, colon cancer, significant changes in diet, and combinations thereof. 20. The method of claim 19. Any one of claims 18-20, wherein the non-responder has one or more symptoms selected from diarrhea, constipation, abdominal cramps, loose stools, abnormal amounts of gas or bloating, and combinations thereof. The method described in. 22. The method of any one of claims 18-21, wherein at least one antibiotic is administered to the non-responder within a period of time prior to the anti-PD-L1 or anti-PD-1 cancer therapy. 23. The method of claim 22, wherein the at least one antibiotic is vancomycin, neomycin, metronidazole, ampicillin or a combination thereof. 24. A method according to claim 22 or 23, wherein the certain period of time is at least one week. 25. The method of any one of claims 18-24, wherein the non-responder's gastrointestinal microbiota comprises elevated levels of E. coli or bacteria other than Bacteroidetes and Firmicutes compared to a cancer-free subject. . 26. The method of any one of claims 18-25, wherein said anti-PD-L2 antibody is administered for at least one week. The anti-PD-L2 antibody may be administered intraperitoneally, subcutaneously, intramuscularly, intravenously, intrathecally, intracerebrally, orally, nasally, rectally, intravaginally, parenterally, intracisternally, topically, 27. The method according to any one of claims 18 to 26, wherein the method is administered bucally or sublingually. 28. A method according to any one of claims 18 to 27, wherein the cancer therapy is for the treatment of cancer, including solid tumors. 29. A method according to any one of claims 18 to 28, wherein the cancer therapy is for the treatment of adenocarcinoma or colorectal tumors. 30. The method of any one of claims 18-29, wherein administration of an anti-RGMb antibody in combination with anti-PD-1 or anti-PD-L1 cancer therapy results in a synergistic reduction in tumor volume. 31. The method of any one of claims 18-30, wherein the non-responder is a non-responder to anti-PD-1 cancer therapy. 32. The method of any one of claims 18-31, wherein the non-responder is a non-responder to anti-PD-L1 cancer therapy. Use of an anti-PD-L1 or anti-PD-1 cancer therapy in combination with an anti-PD-L2 antibody in the manufacture of a medicament for treating or preventing cancer in a subject, wherein the subject has an anti-PD-L1 or are refractory to anti-PD-1 cancer therapy, use. 34. The use according to claim 33, wherein the anti-PD-L2 antibody administered in combination with the anti-PD-L1 or anti-PD-1 cancer therapy results in a synergistic reduction in tumor volume.