Novel t cell receptors and immune therapy using the same

Abstract

The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular the TAA Serine protease inhibitor Kazal-type 2 (SPINK2). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and SPINK2 binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of SPINK2 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

1 . A T cell transduced with a nucleic acid encoding an antigen recognizing construct comprising
 (1) a first variable region comprising SEQ ID NOS: 1-3 and a second variable region comprising SEQ ID NOS: 7-9, or   (2) a first variable region comprising SEQ ID NOS: 13-15 and a second variable region comprising SEQ ID NOS: 19-21, or   (3) a first variable region comprising SEQ ID NOS: 25-27 and a second variable region comprising SEQ ID NOS: 31-33, or   (4) a first variable region comprising SEQ ID NOS: 37-39 and a second variable region comprising SEQ ID NOS: 43-45, or   (5) a first variable region comprising SEQ ID NOS: 49-51 and a second variable region comprising SEQ ID NOS: 55-57, or   (6) a first variable region comprising SEQ ID NOS: 61-63 and a second variable region comprising SEQ ID NOS: 67-69, or   (7) a first variable region comprising SEQ ID NOS: 73-75 and a second variable region comprising SEQ ID NOS: 79-81, or   (8) a first variable region comprising SEQ ID NOS: 85-87 and a second variable region comprising SEQ ID NOS: 91-93, or   (9) a first variable region comprising SEQ ID NOS: 97-99 and a second variable region comprising SEQ ID NOS: 103-105, or   (10) a first variable region comprising SEQ ID NOS: 109-111 and a second variable region comprising SEQ ID NOS: 115-117.   
     
     
         2 . The T cell of  claim 1 , wherein the antigen recognizing construct comprises
 (1) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 4 comprising SEQ ID NOS: 1-3 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 10 comprising SEQ ID NOS: 7-9, or   (2) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 16 comprising SEQ ID NOS: 13-15 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 22 comprising SEQ ID NOS: 19-21, or   (3) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 28 comprising SEQ ID NOS: 25-27 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 34 comprising SEQ ID NOS: 31-33, or   (4) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 40 comprising SEQ ID NOS: 37-39 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 46 comprising SEQ ID NOS: 43-45, or   (5) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 52 comprising SEQ ID NOS: 49-51 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 58 comprising SEQ ID NOS: 55-57, or   (6) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 64 comprising SEQ ID NOS: 61-63 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 70 comprising SEQ ID NOS: 67-69, or   (7) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 76 comprising SEQ ID NOS: 73-75 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 82 comprising SEQ ID NOS: 79-81, or   (8) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 88 comprising SEQ ID NOS: 85-87 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 94 comprising SEQ ID NOS: 91-93, or   (9) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 100 comprising SEQ ID NOS: 97-99 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 106 comprising SEQ ID NOS: 103-105, or   (10) the first variable region comprising at least 95% sequence identity to SEQ ID NO: 112 comprising SEQ ID NOS: 109-111 and the second variable region comprising at least 95% sequence identity to SEQ ID NO: 118 comprising SEQ ID NOS: 115-117.   
     
     
         3 . The T cell of  claim 1 , wherein the antigen recognizing construct comprises
 (1) the first variable region comprising SEQ ID NO: 4 and the second variable region comprising SEQ ID NO: 10, or   (2) the first variable region comprising SEQ ID NO: 16 and the second variable region comprising SEQ ID NO: 22, or   (3) the first variable region comprising SEQ ID NO: 28 and the second variable region comprising SEQ ID NO: 34, or   (4) the first variable region comprising SEQ ID NO: 40 and the second variable region comprising SEQ ID NO: 46, or   (5) the first variable region comprising SEQ ID NO: 52 and the second variable region comprising SEQ ID NO: 58, or   (6) the first variable region comprising SEQ ID NO: 64 and the second variable region comprising SEQ ID NO: 70, or   (7) the first variable region comprising SEQ ID NO: 76 and the second variable region comprising SEQ ID NO: 82, or   (8) the first variable region comprising SEQ ID NO: 88 and the second variable region comprising SEQ ID NO: 94, or   (9) the first variable region comprising SEQ ID NO: 100 and the second variable region comprising SEQ ID NO: 106, or   (10) the first variable region comprising SEQ ID NO: 112 and the second variable region comprising SEQ ID NO: 118.   
     
     
         4 . The T cell of  claim 1 , wherein the antigen recognizing construct comprises
 (1) an alpha chain comprising SEQ ID NOS: 1-3 and a beta chain comprising SEQ ID NOS: 7-9 or a gamma chain comprising SEQ ID NOS: 1-3 and a delta chain comprising SEQ ID NOS: 7-9, or   (2) an alpha chain comprising SEQ ID NOS: 13-15 and a beta chain comprising SEQ ID NOS: 19-21 or a gamma chain comprising SEQ ID NOS: 13-15 and a delta chain comprising SEQ ID NOS: 19-21, or   (3) an alpha chain comprising SEQ ID NOS: 25-27 and a beta chain comprising SEQ ID NOS: 31-33 or a gamma chain comprising SEQ ID NOS: 25-27 and a delta chain comprising SEQ ID NOS: 31-33, or   (4) an alpha chain comprising SEQ ID NOS: 37-39 and a beta chain comprising SEQ ID NOS: 43-45 or a gamma chain comprising SEQ ID NOS: 37-39 and a delta chain comprising SEQ ID NOS: 43-45, or   (5) an alpha chain comprising SEQ ID NOS: 49-51 and a beta chain comprising SEQ ID NOS: 55-57 or a gamma chain comprising SEQ ID NOS: 49-51 and a delta chain comprising SEQ ID NOS: 55-57, or   (6) an alpha chain comprising SEQ ID NOS: 61-63 and a beta chain comprising SEQ ID NOS: 67-69 or a gamma chain comprising SEQ ID NOS: 61-63 and a delta chain comprising SEQ ID NOS: 67-69, or   (7) an alpha chain comprising SEQ ID NOS: 73-75 and a beta chain comprising SEQ ID NOS: 79-81 or a gamma chain comprising SEQ ID NOS: 73-75 and a delta chain comprising SEQ ID NOS: 79-81, or   (8) an alpha chain comprising SEQ ID NOS: 85-87 and a beta chain comprising SEQ ID NOS: 91-93 or a gamma chain comprising SEQ ID NOS: 85-87 and a delta chain comprising SEQ ID NOS: 91-93, or   (9) an alpha chain comprising SEQ ID NOS: 97-99 and a beta chain comprising SEQ ID NOS: 103-105 or a gamma chain comprising SEQ ID NOS: 97-99 and a delta chain comprising SEQ ID NOS: 103-105, or   (10) an alpha chain comprising SEQ ID NOS: 109-111 and a beta chain comprising SEQ ID NOS: 115-117 or a gamma chain comprising SEQ ID NOS: 109-111 and a delta chain comprising SEQ ID NOS: 115-117.   
     
     
         5 . The T cell of  claim 4 , wherein
 (1) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 5 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 11, or   (2) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 17 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 23, or   (3) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 29 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 35, or   (4) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 41 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 47, or   (5) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 53 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 59, or   (6) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 65 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 71, or   (7) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 77 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 83, or   (8) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 89 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 95, or   (9) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 101 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 107, or   (10) the alpha chain further comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 113 and the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 119.   
     
     
         6 . The T cell of  claim 4 , wherein
 (1) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 5 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 11, or   (2) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 17 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 23, or   (3) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 29 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 35, or   (4) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 41 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 47, or   (5) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 53 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 59, or   (6) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 65 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 71, or   (7) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 77 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 83, or   (8) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 89 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 95, or   (9) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 101 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 107, or   (10) the alpha chain further comprises an alpha constant domain comprising SEQ ID NO: 113 and the beta chain further comprises a beta constant domain comprising SEQ ID NO: 119.   
     
     
         7 . The T cell of  claim 4 , wherein
 (1) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 6 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 12, or   (2) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 18 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 24, or   (3) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 30 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 36, or   (4) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 42 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 48, or   (5) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 54 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 60, or   (6) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 66 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 72, or   (7) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 78 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 84, or   (8) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 90 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 96, or   (9) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 102 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 108, or   (10) the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 114 and the beta chain comprises at least 95% sequence identity to SEQ ID NO: 120.   
     
     
         8 . The T cell of  claim 4 , wherein
 (1) the alpha chain comprises SEQ ID NO: 6 and the beta chain comprises SEQ ID NO: 12, or   (2) the alpha chain comprises SEQ ID NO: 18 and the beta chain comprises SEQ ID NO: 24, or   (3) the alpha chain comprises SEQ ID NO: 30 and the beta chain comprises SEQ ID NO: 36, or   (4) the alpha chain comprises SEQ ID NO: 42 and the beta chain comprises SEQ ID NO: 48, or   (5) the alpha chain comprises SEQ ID NO: 54 and the beta chain comprises SEQ ID NO: 60, or   (6) the alpha chain comprises SEQ ID NO: 66 and the beta chain comprises SEQ ID NO: 72, or   (7) the alpha chain comprises SEQ ID NO: 78 and the beta chain comprises SEQ ID NO: 84, or   (8) the alpha chain comprises SEQ ID NO: 90 and the beta chain comprises SEQ ID NO: 96, or   (9) the alpha chain comprises SEQ ID NO: 102 and the beta chain comprises SEQ ID NO: 108, or   (10) the alpha chain comprises SEQ ID NO: 114 and the beta chain comprises SEQ ID NO: 120.   
     
     
         9 . The T cell of  claim 1 , wherein the antigen recognizing construct binds to a peptide consisting of the amino acid sequence of ALSVLRLAL (SEQ ID NO: 133) in a complex with an MHC class I molecule. 
     
     
         10 . The T cell of  claim 1 , wherein the antigen recognizing construct comprises
 (1) the CDR1α comprising SEQ ID NO: 1, the CDR2α comprising SEQ ID NO: 2, the CDR3α comprising SEQ ID NO: 3, the CDR1β comprising SEQ ID NO: 7, the CDR2β comprising SEQ ID NO: 8, and the CDR3β comprising SEQ ID NO: 9, or   (2) the CDR1α comprising SEQ ID NO: 13, the CDR2α comprising SEQ ID NO: 14, the CDR3α comprising SEQ ID NO: 15, the CDR1β comprising SEQ ID NO: 19, the CDR2β comprising SEQ ID NO: 20, and the CDR3β comprising SEQ ID NO: 21, or   (3) the CDR1α comprising SEQ ID NO: 25, the CDR2α comprising SEQ ID NO: 26, the CDR3α comprising SEQ ID NO: 27, the CDR1β comprising SEQ ID NO: 31, the CDR2β comprising SEQ ID NO: 32, and the CDR3β comprising SEQ ID NO: 33, or   (4) the CDR1α comprising SEQ ID NO: 37, the CDR2α comprising SEQ ID NO: 38, the CDR3α comprising SEQ ID NO: 39, the CDR1β comprising SEQ ID NO:   43, the CDR2β comprising SEQ ID NO: 44, and the CDR3β comprising SEQ ID NO: 45, or   (5) the CDR1α comprising SEQ ID NO: 49, the CDR2α comprising SEQ ID NO: 50, the CDR3α comprising SEQ ID NO: 51, the CDR1β comprising SEQ ID NO: 55, the CDR2β comprising SEQ ID NO: 56, and the CDR3β comprising SEQ ID NO: 57, or   (6) the CDR1α comprising SEQ ID NO: 61, the CDR2α comprising SEQ ID NO: 62, the CDR3α comprising SEQ ID NO: 63, the CDR1β comprising SEQ ID NO: 67, the CDR2β comprising SEQ ID NO: 68, and the CDR3β comprising SEQ ID NO: 69, or   (7) the CDR1α comprising SEQ ID NO: 73, the CDR2α comprising SEQ ID NO: 74, the CDR3α comprising SEQ ID NO: 75, the CDR1β comprising SEQ ID NO: 79, the CDR2β comprising SEQ ID NO: 80, and the CDR3β comprising SEQ ID NO: 81, or   (8) the CDR1α comprising SEQ ID NO: 85, the CDR2α comprising SEQ ID NO: 86, the CDR3α comprising SEQ ID NO: 87, the CDR1β comprising SEQ ID NO: 91, the CDR2β comprising SEQ ID NO: 92, and the CDR3β comprising SEQ ID NO: 93, or   (9) the CDR1α comprising SEQ ID NO: 97, the CDR2α comprising SEQ ID NO: 98, the CDR3α comprising SEQ ID NO: 99, the CDR1β comprising SEQ ID NO: 103, the CDR2β comprising SEQ ID NO: 104, and the CDR3β comprising SEQ ID NO: 105, or   (10) the CDR1α comprising SEQ ID NO: 109, the CDR2α comprising SEQ ID NO: 110, the CDR3α comprising SEQ ID NO: 111, the CDR1β comprising SEQ ID NO: 115, the CDR2β comprising SEQ ID NO: 116, and the CDR3β comprising SEQ ID NO: 117.   
     
     
         11 . The T cell of  claim 10 , wherein the antigen recognizing construct binds to a peptide consisting of the amino acid sequence of ALSVLRLAL (SEQ ID NO: 133) in a complex with an MHC class I molecule. 
     
     
         12 . The T cell of  claim 1 , wherein the antigen recognizing construct comprises
 (1) the CDR1α consisting of SEQ ID NO: 1, the CDR2α consisting of SEQ ID NO: 2, the CDR3α comprising SEQ ID NO: 3, the CDR113 consisting of SEQ ID NO: 7, the CDR2β consisting of SEQ ID NO: 8, and the CDR3β comprising SEQ ID NO: 9, or   (2) the CDR1α consisting of SEQ ID NO: 13, the CDR2α consisting of SEQ ID NO: 14, the CDR3α comprising SEQ ID NO: 15, the CDR1β consisting of SEQ ID NO: 19, the CDR2β consisting of SEQ ID NO: 20, and the CDR3β comprising SEQ ID NO: 21, or   (3) the CDR1α consisting of SEQ ID NO: 25, the CDR2α consisting of SEQ ID NO: 26, the CDR3α comprising SEQ ID NO: 27, the CDR1β consisting of SEQ ID NO: 31, the CDR2β consisting of SEQ ID NO: 32, and the CDR3β comprising SEQ ID NO: 33, or   (4) the CDR1α consisting of SEQ ID NO: 37, the CDR2α consisting of SEQ ID NO: 38, the CDR3α comprising SEQ ID NO: 39, the CDR1β consisting of SEQ ID NO: 43, the CDR2β consisting of SEQ ID NO: 44, and the CDR3β comprising SEQ ID NO: 45, or   (5) the CDR1α consisting of SEQ ID NO: 49, the CDR2α consisting of SEQ ID NO: 50, the CDR3α comprising SEQ ID NO: 51, the CDR1β consisting of SEQ ID NO: 55, the CDR2β consisting of SEQ ID NO: 56, and the CDR3β comprising SEQ ID NO: 57, or   (6) the CDR1α consisting of SEQ ID NO: 61, the CDR2α consisting of SEQ ID NO: 62, the CDR3α comprising SEQ ID NO: 63, the CDR1β consisting of SEQ ID NO: 67, the CDR2β consisting of SEQ ID NO: 68, and the CDR3β comprising SEQ ID NO: 69, or   (7) the CDR1α consisting of SEQ ID NO: 73, the CDR2α consisting of SEQ ID NO: 74, the CDR3α comprising SEQ ID NO: 75, the CDR1β consisting of SEQ ID NO: 79, the CDR2β consisting of SEQ ID NO: 80, and the CDR3β comprising SEQ ID NO: 81, or   (8) the CDR1α consisting of SEQ ID NO: 85, the CDR2α consisting of SEQ ID NO: 86, the CDR3α comprising SEQ ID NO: 87, the CDR1β consisting of SEQ ID NO: 91, the CDR2β consisting of SEQ ID NO: 92, and the CDR3β comprising SEQ ID NO: 93, or   (9) the CDR1α consisting of SEQ ID NO: 97, the CDR2α consisting of SEQ ID NO: 98, the CDR3α comprising SEQ ID NO: 99, the CDR1β consisting of SEQ ID NO: 103, the CDR2β consisting of SEQ ID NO: 104, and the CDR3β comprising SEQ ID NO: 105, or   (10) the CDR1α consisting of SEQ ID NO: 109, the CDR2α consisting of SEQ ID NO: 110, the CDR3α comprising SEQ ID NO: 111, the CDR1β consisting of SEQ ID NO: 115, the CDR2β consisting of SEQ ID NO: 116, and the CDR3β comprising SEQ ID NO: 117.   
     
     
         13 . The T cell of  claim 1 , wherein the antigen recognizing construct comprises
 (1) the CDR1α comprising SEQ ID NO: 1, the CDR2α consisting of SEQ ID NO: 2, the CDR3α comprising SEQ ID NO: 3, the CDR113 comprising SEQ ID NO: 7, the CDR2β consisting of SEQ ID NO: 8, and the CDR3β comprising SEQ ID NO: 9, or   (2) the CDR1α comprising SEQ ID NO: 13, the CDR2α consisting of SEQ ID NO: 14, the CDR3α comprising SEQ ID NO: 15, the CDR1β comprising SEQ ID NO: 19, the CDR2β consisting of SEQ ID NO: 20, and the CDR3β comprising SEQ ID NO: 21, or   (3) the CDR1α comprising SEQ ID NO: 25, the CDR2a consisting of SEQ ID NO: 26, the CDR3α comprising SEQ ID NO: 27, the CDR1β comprising SEQ ID NO: 31, the CDR2β consisting of SEQ ID NO: 32, and the CDR3β comprising SEQ ID NO: 33, or   (4) the CDR1α comprising SEQ ID NO: 37, the CDR2α consisting of SEQ ID NO: 38, the CDR3α comprising SEQ ID NO: 39, the CDR1β comprising SEQ ID NO: 43, the CDR2β consisting of SEQ ID NO: 44, and the CDR3β comprising SEQ ID NO: 45, or   (5) the CDR1α comprising SEQ ID NO: 49, the CDR2α consisting of SEQ ID NO: 50, the CDR3α comprising SEQ ID NO: 51, the CDR1β comprising SEQ ID NO: 55, the CDR2β consisting of SEQ ID NO: 56, and the CDR3β comprising SEQ ID NO: 57, or   (6) the CDR1α comprising SEQ ID NO: 61, the CDR2α consisting of SEQ ID NO: 62, the CDR3α comprising SEQ ID NO: 63, the CDR1β comprising SEQ ID NO: 67, the CDR2β consisting of SEQ ID NO: 68, and the CDR3β comprising SEQ ID NO: 69, or   (7) the CDR1α comprising SEQ ID NO: 73, the CDR2α consisting of SEQ ID NO: 74, the CDR3α comprising SEQ ID NO: 75, the CDR1β comprising SEQ ID NO: 79, the CDR2β consisting of SEQ ID NO: 80, and the CDR3β comprising SEQ ID NO: 81, or   (8) the CDR1α comprising SEQ ID NO: 85, the CDR2α consisting of SEQ ID NO: 86, the CDR3α comprising SEQ ID NO: 87, the CDR1β comprising SEQ ID NO: 91, the CDR2β consisting of SEQ ID NO: 92, and the CDR3β comprising SEQ ID NO: 93, or   (9) the CDR1α comprising SEQ ID NO: 97, the CDR2α consisting of SEQ ID NO: 98, the CDR3α comprising SEQ ID NO: 99, the CDR1β comprising SEQ ID NO: 103, the CDR2β consisting of SEQ ID NO: 104, and the CDR3β comprising SEQ ID NO: 105, or   (10) the CDR1α comprising SEQ ID NO: 109, the CDR2α consisting of SEQ ID NO: 110, the CDR3α comprising SEQ ID NO: 111, the CDR1β comprising SEQ ID NO: 115, the CDR2β consisting of SEQ ID NO: 116, and the CDR3β comprising SEQ ID NO: 117.   
     
     
         14 . The T cell of  claim 1 , wherein the antigen recognizing construct comprises
 (1) the CDR1α consisting of SEQ ID NO: 1, the CDR2α comprising SEQ ID NO: 2, the CDR3α consisting of SEQ ID NO: 3, the CDR1β consisting of SEQ ID NO: 7, the CDR2β comprising SEQ ID NO: 8, and the CDR3β consisting of SEQ ID NO: 9, or   (2) the CDR1α consisting of SEQ ID NO: 13, the CDR2α comprising SEQ ID NO: 14, the CDR3α consisting of SEQ ID NO: 15, the CDR1β consisting of SEQ ID NO: 19, the CDR2β comprising SEQ ID NO: 20, and the CDR3β consisting of SEQ ID NO: 21, or   (3) the CDR1α consisting of SEQ ID NO: 25, the CDR2α comprising SEQ ID NO: 26, the CDR3α consisting of SEQ ID NO: 27, the CDR1β consisting of SEQ ID NO: 31, the CDR2β comprising SEQ ID NO: 32, and the CDR3β consisting of SEQ ID NO: 33, or   (4) the CDR1α consisting of SEQ ID NO: 37, the CDR2α comprising SEQ ID NO: 38, the CDR3α consisting of SEQ ID NO: 39, the CDR1β consisting of SEQ ID NO: 43, the CDR2β comprising SEQ ID NO: 44, and the CDR3β consisting of SEQ ID NO: 45, or   (5) the CDR1α consisting of SEQ ID NO: 49, the CDR2α comprising SEQ ID NO: 50, the CDR3α consisting of SEQ ID NO: 51, the CDR1β consisting of SEQ ID NO: 55, the CDR2β comprising SEQ ID NO: 56, and the CDR3β consisting of SEQ ID NO: 57, or   (6) the CDR1α consisting of SEQ ID NO: 61, the CDR2α comprising SEQ ID NO: 62, the CDR3α consisting of SEQ ID NO: 63, the CDR1β consisting of SEQ ID NO: 67, the CDR2β comprising SEQ ID NO: 68, and the CDR3β consisting of SEQ ID NO: 69, or   (7) the CDR1α consisting of SEQ ID NO: 73, the CDR2α comprising SEQ ID NO: 74, the CDR3α consisting of SEQ ID NO: 75, the CDR1β consisting of SEQ ID NO: 79, the CDR2β comprising SEQ ID NO: 80, and the CDR3β consisting of SEQ ID NO: 81, or   (8) the CDR1α consisting of SEQ ID NO: 85, the CDR2α comprising SEQ ID NO: 86, the CDR3α consisting of SEQ ID NO: 87, the CDR1β consisting of SEQ ID NO: 91, the CDR2β comprising SEQ ID NO: 92, and the CDR3β consisting of SEQ ID NO: 93, or   (9) the CDR1α consisting of SEQ ID NO: 97, the CDR2α comprising SEQ ID NO: 98, the CDR3α consisting of SEQ ID NO: 99, the CDR1β consisting of SEQ ID NO: 103, the CDR2β comprising SEQ ID NO: 104, and the CDR3β consisting of SEQ ID NO: 105, or   (10) the CDR1α consisting of SEQ ID NO: 109, the CDR2α comprising SEQ ID NO: 110, the CDR3α consisting of SEQ ID NO: 111, the CDR1β consisting of SEQ ID NO: 115, the CDR2β comprising SEQ ID NO: 116, and the CDR3β consisting of SEQ ID NO: 117.   
     
     
         15 . The T cell of  claim 1 , wherein the antigen recognizing construct comprises
 (1) the CDR1α consisting of SEQ ID NO: 1, the CDR2α consisting of SEQ ID NO: 2, the CDR3α consisting of SEQ ID NO: 3, the CDR1β consisting of SEQ ID NO: 7, the CDR2β consisting of SEQ ID NO: 8, and the CDR3β consisting of SEQ ID NO: 9, or   (2) the CDR1α consisting of SEQ ID NO: 13, the CDR2α consisting of SEQ ID NO: 14, the CDR3α consisting of SEQ ID NO: 15, the CDR1β consisting of SEQ ID NO: 19, the CDR2β consisting of SEQ ID NO: 20, and the CDR3β consisting of SEQ ID NO: 21, or   (3) the CDR1α consisting of SEQ ID NO: 25, the CDR2α consisting of SEQ ID NO: 26, the CDR3α consisting of SEQ ID NO: 27, the CDR1β consisting of SEQ ID NO: 31, the CDR2β consisting of SEQ ID NO: 32, and the CDR3β consisting of SEQ ID NO: 33, or   (4) the CDR1α consisting of SEQ ID NO: 37, the CDR2α consisting of SEQ ID NO: 38, the CDR3α consisting of SEQ ID NO: 39, the CDR1β consisting of SEQ ID NO: 43, the CDR2β consisting of SEQ ID NO: 44, and the CDR3β consisting of SEQ ID NO: 45, or   (5) the CDR1α consisting of SEQ ID NO: 49, the CDR2α consisting of SEQ ID NO: 50, the CDR3α consisting of SEQ ID NO: 51, the CDR1β consisting of SEQ ID NO: 55, the CDR2β consisting of SEQ ID NO: 56, and the CDR3β consisting of SEQ ID NO: 57, or   (6) the CDR1α consisting of SEQ ID NO: 61, the CDR2α consisting of SEQ ID NO: 62, the CDR3α consisting of SEQ ID NO: 63, the CDR1β consisting of SEQ ID NO: 67, the CDR2β consisting of SEQ ID NO: 68, and the CDR3β consisting of SEQ ID NO: 69, or   (7) the CDR1α consisting of SEQ ID NO: 73, the CDR2α consisting of SEQ ID NO: 74, the CDR3α consisting of SEQ ID NO: 75, the CDR1β consisting of SEQ ID NO: 79, the CDR2β consisting of SEQ ID NO: 80, and the CDR3β consisting of SEQ ID NO: 81, or   (8) the CDR1α consisting of SEQ ID NO: 85, the CDR2α consisting of SEQ ID NO: 86, the CDR3α consisting of SEQ ID NO: 87, the CDR1β consisting of SEQ ID NO: 91, the CDR2β consisting of SEQ ID NO: 92, and the CDR3β consisting of SEQ ID NO: 93, or   (9) the CDR1α consisting of SEQ ID NO: 97, the CDR2α consisting of SEQ ID NO: 98, the CDR3α consisting of SEQ ID NO: 99, the CDR1β consisting of SEQ ID NO: 103, the CDR2β consisting of SEQ ID NO: 104, and the CDR3β consisting of SEQ ID NO: 105, or   (10) the CDR1α consisting of SEQ ID NO: 109, the CDR2α consisting of SEQ ID NO: 110, the CDR3α consisting of SEQ ID NO: 111, the CDR1β consisting of SEQ ID NO: 115, the CDR2β consisting of SEQ ID NO: 116, and the CDR3β consisting of SEQ ID NO: 117.   
     
     
         16 . The T cell of  claim 1 , wherein the antigen recognizing construct comprises
 (1) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 4 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 4; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 10 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 10, or   (2) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 16 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 16; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 22 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 22, or   (3) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 28 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 28; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 34 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 34, or   (4) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 40 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 40; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 46 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 46, or   (5) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 52 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 52; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 58 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 58, or   (6) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 64 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 64; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 70 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 70, or   (7) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 76 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 76; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 82 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 82, or   (8) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 88 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 88; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 94 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 94, or   (9) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 100 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 100; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 106 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 106, or   (10) the first variable region comprising at least 90% sequence identity to SEQ ID NO: 112 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 112; and the second variable region comprising at least 90% sequence identity to SEQ ID NO: 118 and the CDR1, CDR2 and CDR3 of SEQ ID NO: 118.   
     
     
         17 . The T cell of  claim 1 , wherein the antigen recognizing construct specifically binds to a SPINK2-001 peptide-MHC molecule complex, wherein the SPINK2-001 peptide consists of the amino acid sequence of ALSVLRLAL (SEQ ID NO: 133), and wherein the MHC molecule is an HLA class I molecule. 
     
     
         18 . The T cell of  claim 1 , wherein the nucleic acid is operably linked to at least one promoter sequence of an expression vector. 
     
     
         19 . The T cell of  claim 1 , wherein the T cell is a CD8+ cell. 
     
     
         20 . The T cell of  claim 1 , wherein the T cell is a CD4+ cell. 
     
     
         21 . A pharmaceutical composition comprising the T cell of  claim 1 .