COMPOSITIONS AND METHODS FOR POTENTIATING IMMUNE CHECKPOINT INHIBITOR THERAPY
The present invention provides compositions and methods for treating a patient having cancer, as well as methods for potentiating an immune checkpoint inhibitor therapy. The methods comprise administering larazotide or a derivative thereof to a subject in need, including subjects undergoing checkpoint inhibitor therapy, and subjects scheduled to undergo immune checkpoint inhibitor therapy.
1 . A method for treating a patient having cancer, comprising administering to a subject undergoing therapy with one or more immune checkpoint inhibitors, an effective amount of larazotide or a derivative thereof.
2 . The method of claim 1 , wherein the immune checkpoint inhibitor targets PD-1, PD-L1, PD-L2, CTLA-4, LAG3, TIM3, and/or IDO.
3 . The method of claim 1 or 2 , wherein the immune checkpoint inhibitor is selected from ipilimumab, tremelimumab, pembrolizumab and nivolumab.
4 . The method of any one of claims 1 to 3 , wherein the subject showed no response or only partial response to prior treatment with an immune checkpoint inhibitor therapy.
5 . The method of claim 4 , wherein the prior immune checkpoint inhibitor therapy was a PD-1 blockade therapy.
6 . The method of any one of claims 1 to 5 , wherein the larazotide, and/or a derivative thereof is administered to the gastrointestinal tract or parenterally.
7 . The method of any one of claims 1 to 6 , wherein the larazotide or derivative is administered to one or more of the duodenum, jejunum, and/or the ileum.
8 . The method of any one of claims 1 to 7 , wherein the larazotide or derivative is administered to the large intestine.
9 . The method of any one of claims 1 to 8 , wherein the larazotide or derivative is administered as delayed release capsules.
10 . The method of claim 9 , wherein the larazotide or derivative is administered in a sustained release formulation.
11 . The method of claim 9 or 10 , wherein the composition is administered from 1 to 3 times per day.
12 . The method of claim 11 , wherein the composition is administered throughout a checkpoint inhibitor therapy regimen, and optionally continued after the regimen.
13 . The method of any one of the preceding claims, wherein the larazotide or derivative is administered as a larazotide-producing probiotic strain or larazotide-encoding bacteriophage.
14 . The method of claim 12 , wherein the composition is administered for at least one week prior to initiation of checkpoint inhibitor therapy.
15 . A method for potentiating immune checkpoint inhibitor therapy comprising administering to a subject in need thereof a therapeutically effective amount of larazotide, and/or a derivative thereof and an immune checkpoint inhibitor regimen.
16 . The method of claim 15 , wherein the subject has been diagnosed with cancer or is at risk for cancer.
17 . The method of claim 16 , wherein the immune checkpoint inhibitor targets PD-1, PD-L1, PD-L2, CTLA-4, LAG3, TIM3, and/or IDO.
18 . The method of claim 17 , wherein the immune checkpoint inhibitor is selected from ipilimumab, tremelimumab, pembrolizumab and nivolumab.
19 . The method of any one of claims 15 to 18 , wherein the subject showed no response or only a partial response to prior treatment with immune checkpoint inhibitor therapy.
20 . The method of claim 19 , wherein the prior immune checkpoint inhibitor therapy was a PD-1 blockade therapy.
21 . The method of any one of claims 15 to 20 , wherein the larazotide and/or a derivative thereof is administered to the gastrointestinal tract or parenterally.
22 . The method of claim 21 , wherein the larazotide or derivative is administered to one or more of the duodenum, jejunum, and/or the ileum.
23 . The method of claim 21 or 22 , wherein the larazotide or derivative is administered to the large intestine.
24 . The method of any one of claims 15 to 23 , wherein the larazotide or derivative is administered as delayed release capsules.
25 . The method of claim 24 , wherein the larazotide or derivative is administered in a sustained release formulation.
26 . The method of claim 24 or 25 , wherein the composition is administered from 1 to 3 times per day.
27 . The method of claim 26 , wherein the composition is administered throughout a checkpoint inhibitor therapy regimen, and optionally continued after the regimen.
28 . The method of any one of claims 15 to 27 , wherein the larazotide or derivative is administered as a larazotide-producing probiotic strain or larazotide-encoding bacteriophage.
29 . The method of any one of claims 15 to 28 , wherein the composition is administered for at least one week prior to initiation of checkpoint inhibitor therapy.