Icos critically regulates the expansion and function of inflammatory human th17 cells

Abstract

The invention includes compositions and methods for generating and expanding therapeutic Th17 cells. The invention includes contacting T cells with a composition comprising a first agent that is capable of providing a primary activation signal to T cells and a second agent that is capable of activating ICOS on T cells in the presence of Th-17 polarizing agents.

1 . A composition comprising a first agent that is capable of providing a primary activation signal to a T cell and a second agent that is capable of activating ICOS on said T cell. 
     
     
         2 - 6 . (canceled) 
     
     
         7 . The composition of  claim 1 , wherein said first agent binds CD3 or a component of the TCR/CD3 complex. 
     
     
         8 . The composition of  claim 1 , wherein said second agent is anti-ICOS antibody or ICOS-L. 
     
     
         9 - 13 . (canceled) 
     
     
         14 . A method for activating or stimulating a population of T cells, said method comprising: 1) providing a population of cells wherein at least a portion thereof comprises T cells; 2) contacting said population of cells with a composition comprising a first agent that is capable of providing a primary activation signal to said T cells and a second agent that is capable of activating ICOS on said T cells. 
     
     
         15 . The method of  claim 14 , wherein said contacting said population of cells with a composition comprising a first agent that is capable of providing a primary activation signal to said T cells and a second agent that is capable of activating ICOS on said T cells is in the presence of a Th-17 polarizing agent. 
     
     
         16 . The method of  claim 15 , wherein said Th-17 polarizing agent is selected from the group consisting of IL-1β, IL-6, neutralizing anti-IFNγ, anti-IL-4, and any combination thereof. 
     
     
         17 . The method of  claim 14 , wherein said composition comprises a solid phase surface. 
     
     
         18 . The method of  claim 14 , wherein said composition comprises a human cell line. 
     
     
         19 . The method of  claim 18 , wherein said human cell line is selected from the group consisting of K562, U937, 721.221, T2, and C1R cells. 
     
     
         20 . The method of  claim 18 , wherein said cell is genetically modified to express a human Fc7 receptor. 
     
     
         21 . The method of  claim 20 , wherein said Fc7 receptor is selected from the group consisting of CD32, CD64, and any combination thereof. 
     
     
         22 . The method of  claim 14 , wherein said first agent binds CD3 or a component of the TCR/CD3 complex. 
     
     
         23 . The method of  claim 14 , wherein said second agent is anti-ICOS antibody or ICOS-L. 
     
     
         24 - 32 . (canceled) 
     
     
         33 . A method of immunotherapy comprising administering an ICOS stimulated T cell to a patient in need thereof. 
     
     
         34 . The method of  claim 33 , wherein said ICOS stimulated T cell has been contacted with a first agent that is capable of providing a primary activation signal to T cells and a second agent that is capable of activating ICOS on T cells in the presence of a Th-17 polarizing agent. 
     
     
         35 . The method of  claim 34 , wherein said Th-17 polarizing agent is selected from the group consisting of IL-1β, IL-6, neutralizing anti-IFNγ, anti-IL-4, and any combination thereof. 
     
     
         36 . The method of  claim 34 , wherein said first agent binds CD3 or a component of the TCR/CD3 complex. 
     
     
         37 . The method of  claim 34 , wherein said second agent is anti-ICOS antibody or ICOS-L. 
     
     
         38 . The method of  claim 34 , wherein said Th17 has been contacted with an antigen. 
     
     
         39 . (canceled) 
     
     
         40 . A method of regulating a Th17 cell in a mammal, said method comprising administering to said mammal an effective amount of the composition of  claim 1 .