Modulation of the immune response

Abstract

Described herein are compositions and methods for the modulation of T-cell tolerance, which can be upregulated or down regulated by concurrent enhancement or inhibition of CEACAM1/TIM3 interactions. As described herein, the discovery that CEACAM1 is a direct ligand of TIM3 and vice versa has been shown in cis and in trans. In addition, as demonstrated herein, CEACAM1 and TIM3 are co-regulated during the course of T-cell activation.

1 - 33 . (canceled) 
     
     
         34 . A composition for modulating T cell tolerance, the composition comprising an agent that modulates the interaction of CEACAM1 with TIM3, wherein the agent comprises a proteo-mimetic of CEACAM1 that binds to TIM3, and wherein the agent inhibits the interaction of CEACAM1 with TIM3 and inhibits T cell tolerance. 
     
     
         35 . The composition of  claim 34 , wherein the proteo-mimetic activates or inhibits signaling mediated by the interaction of TIM3 and CEACAM1. 
     
     
         36 . A composition for modulating T cell tolerance, the composition comprising an agent that modulates the interaction of CEACAM1 with TIM3, wherein the agent comprises a proteo-mimetic of CEACAM1 that binds to TIM3 and a proteo-mimetic of TIM3 that binds to CEACAM1, and wherein the agent inhibits the interaction of CEACAM1 with TIM3 and inhibits T cell tolerance. 
     
     
         37 . A method of modulating T cell tolerance, the method comprising administering an agent that modulates the interaction of TIM3 with CEACAM 1, wherein the agent inhibits the interaction of TIM3 with CEACAM1 and inhibits T cell tolerance. 
     
     
         38 . The method of  claim 37 , wherein the agent comprises a proteo-mimetic of TIM3 that binds to CEACAM1. 
     
     
         39 . The method of  claim 37 , wherein the proteo-mimetic of TIM3 that binds to CEACAM1 comprises SEQ ID NO: 30 or SEQ ID NO: 31. 
     
     
         40 . The method of  claim 37 , wherein the proteo-mimetic binds to CEACAM1 and activates or inhibits signaling mediated by the interaction of TIM3 and CEACAM1. 
     
     
         41 . The method of  claim 37 , wherein the agent comprises a proteo-mimetic of CEACAM1 that binds to TIM3. 
     
     
         42 . The method of  claim 37 , wherein the proteo-mimetic binds to TIM3 and activates or inhibits signaling mediated by the interaction of TIM3 and CEACAM1. 
     
     
         43 . The method of  claim 37 , wherein the agent comprises a proteo-mimetic of CEACAM1 that binds to TIM3 and a proteo-mimetic of TIM3 that binds to CEACAM1.