Soluble mic neutralizing monoclonal antibody for treating cancer

Abstract

Described herein are compositions and methods relating to antibodies that bind soluble MIC (sMIC), e.g. for the treatment of MIC-positive cancers.

What is claimed: 
     
         1 . A first isolated antibody or antigen-binding portion thereof that competes for binding to a sMIC polypeptide with a second antibody comprising:
 a. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 9;   b. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 10;   c. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 11;   d. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 12;   e. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 13; and   f. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 14;   
     
     
         2 . The isolated antibody or antigen-binding portion of  claim 1 , wherein the first isolated antibody or antigen-binding portion comprises a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 14. 
     
     
         3 . The isolated antibody or antigen-binding portion of  claim 1 , wherein the first isolated antibody or antigen-binding portion comprises at least one heavy or light chain complementarity determining region (CDR) selected from:
 a. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 9;   b. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 10;   c. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 11;   d. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 12;   e. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 13; and   f. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 14.   
     
     
         4 . The isolated antibody or antigen-binding portion of  claim 1 , wherein the first isolated antibody or antigen-binding portion comprises at the heavy chain complementarity determining regions (CDRs):
 a. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 12;   b. a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 13; and   c. a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 14.   
     
     
         5 . The isolated antibody or antigen-binding portion of  claim 1 , wherein the first isolated antibody or antigen-binding portion comprises light chain complementarity determining regions (CDRs):
 a. a light chain CDR1 having the amino acid sequence of SEQ ID NO: 9;   b. a light chain CDR2 having the amino acid sequence of SEQ ID NO: 10; and   c. a light chain CDR3 having the amino acid sequence of SEQ ID NO: 11.   
     
     
         6 . The isolated antibody or antigen-binding portion thereof of  claim 1 , wherein the antibody or antigen-binding portion thereof is selected from the group consisting of:
 an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, a scFv, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, and a bispecific antibody.   
     
     
         7 . The isolated antibody or antigen-binding portion thereof of  claim 1 , comprising a light chain having the sequence of SEQ ID NO: 7. 
     
     
         8 . The isoalted antibody or antigen-binding portion thereof of  claim 7 , further comprising a conservative substitution in a sequence not comprised by a CDR. 
     
     
         9 . The antibody or antigen-binding portion thereof of  claim 1 , comprising a heavy chain having the sequence of SEQ ID NO: 8. 
     
     
         10 . The antibody or antigen-binding portion thereof of  claim 9 , further comprising a conservative substitution in a sequence not comprised by a CDR. 
     
     
         11 . The isolated antibody or antibody-binding portion thereof of  claim 1 , wherein the isolated antibody or antigen-binding portion thereof binds specifically to sMIC. 
     
     
         12 . A pharmaceutical composition comprising an antibody or antigen-binding portion thereof of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         13 . A nucleic acid encoding an antibody or antigen-binding portion thereof of  claim 1 . 
     
     
         14 . The nucleic acid of  claim 13 , wherein one or more of the nucleic acid sequences encoding the CDRs of the antibody or antigen-binding portion thereof are selected from the group consisting of SEQ ID NOs: 1-6. 
     
     
         15 . The nucleic acid of  claim 13 , wherein the nucleic acid is a cDNA. 
     
     
         16 . A method of inhibiting sMIC, the method comprising contacting a cell with or administering to a subject an antibody or antigen-binding portion thereof of  claim 1 . 
     
     
         17 . A method of treating a MIC-positive cancer in a subject in need thereof, the method comprising administering an effective amount of a pharmaceutical composition of  claim 12  to the subject. 
     
     
         18 . The method of  claim 17 , wherein the MIC-positive cancer is an epithelial cell tumor. 
     
     
         19 . The method of  claim 17 , wherein the MIC-positive cancer is a hematopoietic malignancy. 
     
     
         20 . The method of  claim 17 , further comprising administering an additional immunotherapy.