Car t-cell therapy directed to lhr for the treatment of solid tumors

Abstract

Provided herein are novel anti-LHR chimeric antigen receptor (CAR), cells or compositions comprising the same, vector or plasmid encoding anti-LHR CAR, and methods for producing the same, or using the same for detecting or treating ovarian cancer or prostate cancer. Also provided herein are anti-LHR antibody, compositions comprising the same, nucleic acid sequence encoding the same, and a kit for detecting LHR.

What is claimed is: 
     
         1 . A chimeric antigen receptor (CAR) comprising:
 (a) an antigen binding domain of an anti-luteinizing hormone receptor (“LHR”) antibody comprising an anti-LHR heavy chain (HC) variable region comprising the amino acid sequence of SEQ ID NO.: 3 or an amino acid sequence having 90% identity thereto and an anti-LHR light chain (LC) variable region comprising the amino acid sequence of SEQ ID NO.: 7 or an amino acid sequence having 90% identity thereto;   (b) a hinge domain;   (c) a transmembrane domain;   (d) a costimulatory signaling region; and   (e) a CD3 zeta signaling domain.   
     
     
         2 . The CAR of  claim 1 , wherein the antigen binding domain comprises a heavy chain (HC) variable region comprising the amino acid sequence of SEQ ID NO.: 3 and an anti-LHR light chain (LC) variable region comprising the amino acid sequence of SEQ ID NO.: 7. 
     
     
         3 . The CAR of  claim 1 , further comprising a detectable marker or a purification marker. 
     
     
         4 . An isolated nucleic acid sequence encoding the CAR of  claim 1 . 
     
     
         5 . The isolated nucleic acid sequence of  claim 4 , further comprising a detectable or purification marker. 
     
     
         6 . An isolated cell comprising the CAR of  claim 1 . 
     
     
         7 . An isolated cell comprising the isolated nucleic acid molecule of  claim 4 . 
     
     
         8 . The isolated cell of  claim 6 , wherein the cell is a T-cell or a, natural killer (NK) cell. 
     
     
         9 . The isolated cell of  claim 8 , wherein the antigen binding domain is expressed on the cell surface of the T-cell or the NK cell. 
     
     
         10 . A method to produce a CAR comprising culture the cell of  claim 4  under conditions to express the isolated nucleic acid. 
     
     
         11 . A method of inhibiting the growth of a cancer cell, comprising contacting the cell with an effective amount of the isolated cell of  claim 8 . 
     
     
         12 . The method of  claim 11 , wherein the cancer cell expresses or overexpresses LHR. 
     
     
         13 . A method of inhibiting the growth of a cancer cell in a subject in need thereof, comprising administering to the subject an effective amount of the isolated cell of  claim 8 . 
     
     
         14 . The method of  claim 13 , wherein the cancer cell expresses or overexpresses LHR. 
     
     
         15 . A kit comprising the CAR of  claim 1 , and instructions for use. 
     
     
         16 . An isolated antibody comprising an anti-LHR heavy chain (HC) variable region comprising the amino acid sequence of SEQ ID NO.: 3 or an amino acid sequence having 90% identity thereto and an anti-LHR light chain (LC) variable region comprising the amino acid sequence of SEQ ID NO.: 7 or an amino acid sequence having 90% identity thereto. 
     
     
         17 . The antibody of  claim 16 , wherein the HC comprises the amino acid sequence of SEQ ID NO.: 3 and the LC comprises the amino acid sequence of SEQ ID NO.: 7. 
     
     
         18 . The isolated antibody of  claim 17 , wherein the antibody is a monoclonal antibody. 
     
     
         19 . An isolated nucleic acid encoding the antibody of  claim 16 . 
     
     
         20 . A method to detect a cell expressing LHR comprising contacting the cell with an antibody of  claim 16  under conditions that favor the binding of the antibody to the cell, wherein the antibody is detectably labeled.