Beta-alethine, immune modulators, and uses thereof

Abstract

The present disclosure provides methods, kits, and compositions comprising β-alethine and one or more immune modulators and methods to determine when they are advantageous. Particular applications include the use of β-alethine and one or more immune modulators in the treatment of cancer.

1 . A method of treating colon cancer in a subject in need thereof, which comprises administering to the subject an effective amount of (1) β-alethine and (2) at least one immune modulator, wherein the administration of β-alethine occurs before, concurrently with, or after the administration of the immune modulator, and wherein the immune modulator comprises an antagonist antibody or antigen-binding fragment thereof that binds to an inhibitory immune checkpoint molecule. 
     
     
         2 - 5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the inhibitory immune checkpoint molecule is selected from the group consisting of: PD-1, PD-L1, CTLA-4, IDO, TIM3, LAG3, TIGIT, BTLA, VISTA, KIRs, and CD39. 
     
     
         7 . The method of  claim 6 , wherein the inhibitory immune checkpoint molecule is PD-1. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 6 , wherein the inhibitory immune checkpoint molecule is CTLA-4. 
     
     
         10 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the immune modulator comprises an anti-PD-1 antibody or antigen-binding fragment thereof. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 1 , wherein the immune modulator comprises an anti-CTLA-4 antibody or antigen-binding fragment thereof. 
     
     
         16 - 32 . (canceled) 
     
     
         33 . The method of  claim 1  further comprising
 i.) identifying a subject with an immune cell or cancer cell sample that has an expression level of the inhibitory immune checkpoint molecule higher than a predetermined value. 
 
     
     
         34 - 50 . (canceled) 
     
     
         51 . A method of inhibiting tumor growth in a subject having colon cancer, the method comprising administering an effective amount of β-alethine into the tumor of the subject, wherein β-alethine is injected into the tumor of the subject before, concurrently with, or after the administration of at least one immune modulator to the subject, and wherein the immune modulator comprises an antagonist antibody or antigen-binding fragment thereof that binds to an inhibitory immune checkpoint molecule. 
     
     
         52 - 55 . (canceled) 
     
     
         56 . The method of  claim 51 , wherein the inhibitory immune checkpoint molecule is selected from the group consisting of: PD-1, PD-L1, CTLA-4, IDO, TIM3, LAG3, TIGIT, BTLA, VISTA, KIRs, and CD39. 
     
     
         57 . (canceled) 
     
     
         58 . The method of  claim 51 , wherein the immune modulator comprises an anti-PD-1 antibody or antigen-binding fragment thereof, or an anti-CTLA-4 antibody or antigen-binding fragment thereof. 
     
     
         59 - 87 . (canceled) 
     
     
         88 . A pharmaceutical kit comprising at least two compartments, one compartment comprising β-alethine and another compartment comprising at least one immune modulator, wherein the immune modulator comprises an anti-PD-1 antibody or antigen-binding fragment thereof or an anti-CTLA-4 antibody or antigen-binding fragment thereof. 
     
     
         89 - 145 . (canceled)