Novel il2 agonists and methods of use thereof

Abstract

The present disclosure relates to IL2 agonists with improved therapeutic profiles.

1 . An IL2 agonist comprising:
 (a) an Fc domain; an   (b) an IL2 moiety C-terminal to the Fc domain, wherein the IL2 moiety comprises an IL2 domain and an IL2-Rα domain.   
     
     
         2 . The IL2 agonist of  claim 1 , wherein the IL2 domain is N-terminal to the IL2-Rα domain. 
     
     
         3 . The IL2 agonist of  claim 1 , wherein the IL2 domain is C-terminal to the IL2-Rα domain. 
     
     
         4 .- 5 . (canceled) 
     
     
         6 . The IL2 agonist of  claim 1 , wherein the IL2 domain and the IL2-Rα domain are connected via a linker (“the IL2 moiety linker”). 
     
     
         7 .- 11 . (canceled) 
     
     
         12 . The IL2 agonist of  claim 1 , wherein the Fc domain and the IL2 moiety are connected via a linker (the “Fc-IL2 linker”). 
     
     
         13 .- 19 . (canceled) 
     
     
         20 . The IL2 agonist  claim 1  which is a dimer. 
     
     
         21 . The IL2 agonist of  claim 20 , which is a homodimer. 
     
     
         22 . The IL2 agonist of  claim 20 , which is a heterodimer. 
     
     
         23 . The IL2 agonist of  claim 1 , which is bivalent for the IL2 moiety. 
     
     
         24 . The IL2 agonist of  claim 1 , which comprises a targeting moiety. 
     
     
         25 . (canceled) 
     
     
         26 . The IL2 agonist of  claim 24 , wherein the targeting moiety:
 (a) binds to a tumor associated antigen;   (b) binds to a tumor microenvironment antigen;   (c) binds to a cell surface molecule of tumor reactive lymphocytes;   (d) binds to a checkpoint inhibitor;   (e) binds to a peptide-MHC complex;   (f) is a peptide-MHC complex; or   (g) binds to an antigen associated with or targeted by an autoimmune response.   
     
     
         27 .- 45 . (canceled) 
     
     
         46 . The IL2 agonist of  claim 26 , wherein the targeting moiety is an antibody or antigen binding fragment thereof. 
     
     
         47 . The IL2 agonist of  claim 46 , wherein the targeting moiety is a Fab or scFv. 
     
     
         48 . (canceled) 
     
     
         49 . The IL2 agonist of  claim 26 , wherein the targeting moiety is a peptide-MHC complex. 
     
     
         50 .- 60 . (canceled) 
     
     
         61 . A nucleic acid or plurality of nucleic acids encoding the IL2 agonist of  claim 1 . 
     
     
         62 . A host cell engineered to express the IL2 agonist of  claim 1 . 
     
     
         63 . A method of producing an IL2 agonist, comprising culturing the host cell of  claim 62  and recovering the IL2 agonist expressed thereby. 
     
     
         64 . A pharmaceutical composition comprising the IL2 agonist of  claim 1  and an excipient. 
     
     
         65 . A method of treating cancer, comprising administering to a subject in need thereof the IL2 agonist of  claim 1 . 
     
     
         66 . A method of treating cancer, comprising administering to a subject in need thereof:
 (a) chimeric antigen receptor (“CAR”) T cells (“CART cells”); and   (b) an IL2 agonist according to  claim 1  comprising a targeting moiety that binds to the T cell receptor of the CART cells or another cell surface molecule on the CART cells.   
     
     
         67 .- 68 . (canceled)