Peptide mimotopes of claudin 18.2 and uses thereof

Abstract

The present invention provides molecules that mimic antigenic determinants of the integral transmembrane protein claudin 18.2 (CLDN18.2). These molecules compete with CLDN18.2 for binding to a CLDN18.2 binding domain, e.g. a CLDN18.2 binding domain of an antibody, and are capable of detecting antibodies against CLDN18.2. The mimotopes of the invention may be used to generate or inhibit immune responses in animals and preferably humans. Furthermore, they can be used for purposes of detecting agents comprising a CLDN18.2 binding domain in biological samples as well as for purifying agents comprising a CLDN18.2 binding domain.

1 . A chimeric antigen receptor comprising a single-chain variable fragment (scFV) fused to a CD3-zeta transmembrane and endodomain,
 wherein said scFV comprises a heavy chain variable region (VH) and a light chain variable region (VL), each comprising a set of three complementarity-determining regions (CDR1, CDR2, and CDR3),   wherein the VH CDR1, CDR2, and CDR3 have the amino acid sequences of positions 45-52, positions 70-77, and positions 116-126 of SEQ ID NO: 12, respectively, and   wherein the VL CDR1, CDR2, and CDR3 have the amino acid sequences of positions 47-58, positions 76-78, and positions 115-123 of SEQ ID NO: 13, respectively.   
     
     
         2 . The chimeric antigen receptor of  claim 1 , wherein the scFV further comprises a peptide linker connecting the VH and VL, wherein the peptide linker comprises the amino acid sequence (GGGGS)3, VE(GGSGGS)2GGVD, (GGGGS)4, (GGGGS)5, or GGGGS(GGS)3GGGS. 
     
     
         3 . The chimeric antigen receptor of  claim 1 , wherein the VH comprises an amino acid sequence represented by SEQ ID NO: 2 and the VL comprises an amino acid sequence represented by SEQ ID NO: 3. 
     
     
         4 . The chimeric antigen receptor of  claim 3 , wherein the scFV further comprises a peptide linker connecting the VH and VL, wherein the peptide linker comprises the amino acid sequence (GGGGS)3, VE(GGSGGS)2GGVD, (GGGGS)4, (GGGGS)5, or GGGGS(GGS)3GGGS. 
     
     
         5 . A recombinant nucleic acid encoding the chimeric antigen receptor of  claim 1 . 
     
     
         6 . The recombinant nucleic acid of  claim 5 , wherein the nucleic acid is RNA. 
     
     
         7 . A recombinant nucleic acid encoding the chimeric antigen receptor of  claim 3 . 
     
     
         8 . The recombinant nucleic acid of  claim 7 , wherein the nucleic acid is RNA. 
     
     
         9 . A cell comprising the chimeric antigen receptor of  claim 1 . 
     
     
         10 . The cell of  claim 9 , wherein the cell is an immune effector cell. 
     
     
         11 . The cell of  claim 9 , wherein the cell is a T cell. 
     
     
         12 . The cell of  claim 11 , wherein the chimeric antigen receptor is on the surface of the T cell. 
     
     
         13 . A cell comprising the chimeric antigen receptor of  claim 3 . 
     
     
         14 . The cell of  claim 13 , wherein the cell is an immune effector cell. 
     
     
         15 . The cell of  claim 13 , wherein the cell is a T cell. 
     
     
         16 . The cell of  claim 15 , wherein the chimeric antigen receptor is on the surface of the T cell. 
     
     
         17 . A method for treating a patient affected from a cancer characterized by cancer cells expressing CLDN18.2 comprising a step of administering to the patient the cell of  claim 9 . 
     
     
         18 . A method for treating a patient affected from a cancer characterized by cancer cells expressing CLDN18.2 comprising a step of administering to the patient the cell of  claim 11 . 
     
     
         19 . A method for treating a patient affected from a cancer characterized by cancer cells expressing CLDN18.2 comprising a step of administering to the patient the cell of  claim 13 . 
     
     
         20 . A method for treating a patient affected from a cancer characterized by cancer cells expressing CLDN18.2 comprising a step of administering to the patient the cell of  claim 15 .