Compositions and methods for potentiating immune checkpoint inhibitor therapy

Abstract

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.

What is claimed is: 
     
         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.