Cd19-targeted chimeric antigen receptor and use thereof

Abstract

A chimeric antigen receptor, comprising an amino acid sequence shown in SEQ ID NO. 1. A nucleic acid encoding the chimeric antigen receptor, a vector comprising the nucleic acid, an immune effector cell comprising the chimeric antigen receptor, the nucleic acid molecule and/or the vector, a method for preparing the immune effector cell, a composition comprising the immune effector cell, and use of the chimeric antigen receptor.

1 . A chimeric antigen receptor, comprising the amino acid sequence shown in SEQ ID NO. 1. 
     
     
         2 . An isolated nucleic acid molecule, encoding the chimeric antigen receptor according to  claim 1 . 
     
     
         3 . An isolated nucleic acid molecule, encoding a chimeric antigen receptor, wherein the nucleic acid molecule comprises the nucleic acid sequence shown in SEQ ID NO. 2. 
     
     
         4 . A vector, comprising the nucleic acid molecule according to  claim 2 . 
     
     
         5 . An immune effector cell, comprising one or more of the following:
 the chimeric antigen receptor according to  claim 1 ,   a nucleic acid molecule encoding the chimeric antigen receptor according to  claim 1 , and   a the vector comprising the nucleic acid molecule encoding the chimeric antigen receptor according to  claim 1 .   
     
     
         6 . The immune effector cell according to  claim 5 , wherein the immune effector cell is selected from the group consisting of a T lymphocyte and a natural killer cell. 
     
     
         7 . The immune effector cell according to  claim 5-6 , wherein the a chimeric antigen receptor comprising an amino acid sequence shown in SEQ ID NO. 1 is expressed on the surface of the cell. 
     
     
         8 . A method for preparing the immune effector cell, comprising the a step of transducing the vector according to  claim 4  into the immune effector cell. 
     
     
         9 . The method according to  claim 8 , wherein the immune effector cell is selected from the group consisting of a T lymphocyte and a natural killer cell. 
     
     
         10 . A composition, comprising the immune effector cell according to  claim 5 . 
     
     
         11 - 18 . (canceled) 
     
     
         19 . A method for treating a disease or disorder associated with CD19 expression, comprising the step of administrating one or more of the following to a patient in need thereof
 the chimeric antigen receptor according to  claim 1 ,   a nucleic acid molecule encoding the chimeric antigen receptor according to  claim 1 ,   a vector comprising the nucleic acid molecule encoding the chimeric antigen receptor according to  claim 1 , and   an immune effector cell comprising one or more of the following: the chimeric antigen receptor according to  claim 1 , the nucleic acid molecule encoding the chimeric antigen receptor according to  claim 1 , and the vector comprising the nucleic acid molecule encoding the chimeric antigen receptor according to  claim 1 .   
     
     
         20 . The method according to  claim 19 , wherein the disease or disorder associated with CD19 expression comprises non-solid tumors. 
     
     
         21 . The method according to  claim 20 , wherein the non-solid tumor comprises leukemia and/or lymphoma. 
     
     
         22 . The method according to  claim 19 , wherein the disease or disorder associated with CD19 expression comprises acute lymphoblastic leukemia and/or B-cell lymphoma. 
     
     
         23 . The method according to  claim 22 , wherein the acute lymphoblastic leukemia comprises acute lymphoblastic leukemia in adults and/or acute lymphoblastic leukemia in children. 
     
     
         24 . The method according to  claim 23 , wherein the step of administrating is administered at a dose of 0.25 × 10 8  to 0.5 × 10 8  CAR-positive T cells. 
     
     
         25 . The method according to  claim 22 , wherein the B-cell lymphoma comprises non-Hodgkin’s lymphoma. 
     
     
         26 . The method according to  claim 25 , wherein the step of administrating is administered at a dose of 1 × 10 8  to 2 × 10 8  CAR-positive T cells. 
     
     
         27 - 34 . (canceled) 
     
     
         35 . The vector according to  claim 4 , wherein the vector is a lentivirus vector. 
     
     
         36 . The composition according to  claim 10 , further comprising one or more formulations of carriers, stabilizers, excipients, diluents, solubilizers, surfactants, emulsifiers and preservatives. 
     
     
         37 . The composition according to  claim 10 , wherein the composition is present in the form of liquid, and frozen or lyophilized composition. 
     
     
         38 . The composition according to  claim 10 , wherein the immune effector cell is selected from the group consisting of a T lymphocyte and a natural killer cell. 
     
     
         39 . The composition according to  claim 10 , wherein a chimeric antigen receptor comprising an amino acid sequence shown in SEQ ID NO. 1 is expressed on the surface of the immune effector cell. 
     
     
         40 . The method according to  claim 23 , wherein the acute lymphoblastic leukemia is relapsed or refractory acute lymphoblastic leukemia. 
     
     
         41 . The method according to  claim 24 , wherein the CAR-positive T cells are administrated in a single dose. 
     
     
         42 . The method according to  claim 24 , wherein the CAR-positive T cells are administrated by intravenous injection. 
     
     
         43 . The method according to  claim 25 , wherein the non-Hodgkin’s lymphoma is relapsed or refractory non-Hodgkin’s lymphoma. 
     
     
         44 . The method according to  claim 26 , wherein the CAR-positive T cells are administrated in a single dose. 
     
     
         45 . The method according to  claim 26 , wherein the CAR-positive T cells are administrated by intravenous injection.