Anti-il1rap antibodies

Abstract

Provided herein are, inter alia, antibodies capable of binding Interleukin-1 receptor accessory protein (IL1RAP). The antibodies provided herein include novel light chain and heavy chain sequences and bind IL1RAP with high efficiency and specificity. The anti-IL1RAP antibodies provided herein are, inter alia, useful for the treatment of IL1RAP-expressing cancers such as AML.

1 .- 80 . (canceled) 
     
     
         81 . An anti-interleukin-1 receptor accessory protein (IL1RAP) antibody comprising a light chain variable domain comprising the sequence of SEQ ID NO:7 and a heavy chain variable domain comprising the sequence of SEQ ID NO:8. 
     
     
         82 . The anti-IL1RAP antibody of  claim 81 , wherein said antibody is a Fab′ fragment. 
     
     
         83 . The anti-IL1RAP antibody of  claim 81 , wherein said antibody is capable of binding IL1RAP with an equilibrium dissociation constant (K D ) of about 21 nM. 
     
     
         84 . The anti-IL1RAP antibody of  claim 81 , wherein said antibody has an EC 50  of about 4.9 ng/ml. 
     
     
         85 . The anti-IL1RAP antibody of  claim 81 , wherein said antibody is bound to an IL1RAP. 
     
     
         86 . An isolated nucleic acid encoding the anti-IL1RAP antibody of  claim 81 . 
     
     
         87 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of the anti-IL1RAP antibody of  claim 81 , thereby treating cancer in said subject. 
     
     
         88 . An anti-interleukin-1 receptor accessory protein (IL1RAP) single chain antibody (scFv) comprising a light chain variable domain comprising the sequence of SEQ ID NO:7 and a heavy chain variable domain comprising the sequence of SEQ ID NO:8. 
     
     
         89 . The anti-IL1RAP scFv of  claim 88 , wherein said scFv comprises the sequence of SEQ ID NO:17. 
     
     
         90 . An isolated nucleic acid encoding the anti-IL1RAP scFv of  claim 88 . 
     
     
         91 . A pharmaceutical composition comprising a therapeutically effective amount of the anti-IL1RAP scFv of  claim 88  and a pharmaceutically acceptable excipient. 
     
     
         92 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of the anti-IL1RAP scFv of  claim 88 , thereby treating cancer in said subject. 
     
     
         93 . A recombinant protein comprising:
 (i) a first single chain variable fragment (scFv) capable of binding an effector cell ligand; and   (ii) a second single chain variable fragment (scFv) capable of binding IL1RAP and comprising a light chain variable domain comprising the sequence of SEQ ID NO:7 and a heavy chain variable domain comprising the sequence of SEQ ID NO:8.   
     
     
         94 . The recombinant protein of  claim 93 , wherein said effector cell ligand is a CD3 protein. 
     
     
         95 . The recombinant protein of  claim 94 , wherein said second scFv comprises the sequence of SEQ ID NO:17. 
     
     
         96 . An isolated nucleic acid encoding the recombinant protein of  claim 93 . 
     
     
         97 . A pharmaceutical composition comprising a therapeutically effective amount of the recombinant protein of  claim 93  and a pharmaceutically acceptable excipient. 
     
     
         98 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of the recombinant protein of  claim 93 , thereby treating cancer in said subject. 
     
     
         99 . A recombinant protein comprising:
 (i) an anti-IL1RAP single chain variable fragment (scFv) comprising a light chain variable domain comprising the sequence of SEQ ID NO:7 and a heavy chain variable domain comprising the sequence of SEQ ID NO:8; and   (ii) a transmembrane domain.   
     
     
         100 . The recombinant protein of  claim 99 , wherein said anti-IL1RAP scFv comprises the sequence of SEQ ID NO:17. 
     
     
         101 . An isolated nucleic acid encoding the recombinant protein of  claim 99 . 
     
     
         102 . A pharmaceutical composition comprising a therapeutically effective amount of the recombinant protein of  claim 99  and a pharmaceutically acceptable excipient. 
     
     
         103 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of the recombinant protein of  claim 99 , thereby treating cancer in said subject. 
     
     
         104 . A method of inhibiting proliferation of a cell, said method comprising:
 (i) contacting a cell with an anti-IL1RAP antibody of  claim 81 , a recombinant protein of  claim 93  or a recombinant protein of  claim 99 , thereby forming a contacted cell; and   (ii) allowing said anti-IL1RAP antibody of  claim 81 , said recombinant protein of  claim 93  or said recombinant protein of  claim 99  to bind an IL1RAP on said contacted cell, thereby inhibiting proliferation of said cell.