Transfected t-cells and t-cell receptors for use in immunotherapy against cancers

Abstract

The present description relates to T-cell receptors (TCRs) binding to tumor-associated antigens (TAAs) for targeting cancer cells, T-cells expressing same, methods for producing same, and methods for treating cancers using same. In particular, the present description relates to TCRs and their variants that bind to HLA class I or II molecules with a peptide, such as IGF2BP3-001 have the amino acid sequence of KIQEILTQV (SEQ ID NO: 1). The present description further relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present description relates to the immunotherapy of cancer. The present description furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T-cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

1 . A method of treating a patient who has cancer that presents on the cell surface a peptide consisting of the amino acid sequence of KIQEILTQV (SEQ ID NO: 1) in complex with HLA-A*02, comprising administering to the patient a population of transformed T cells comprising a nucleic acid or nucleic acids encoding an alpha chain and/or a beta chain,
 wherein
 the alpha chain comprises
 SEQ ID NO: 5, 
 SEQ ID NO: 6, and 
 SEQ ID NO: 7, and 
 
 the beta chain comprises
 SEQ ID NO: 13, 
 SEQ ID NO: 14, and 
 SEQ ID NO: 15, and 
 
   wherein the cancer is selected from non-small cell lung cancer, small cell lung cancer, renal cell cancer, glioblastoma, gastric cancer, colorectal cancer, hepatocellular cancer, pancreatic cancer, chronic lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, melanoma, ovarian cancer, uterine cancer, and esophageal cancer.   
     
     
         2 . The method of  claim 1 , wherein
 the alpha chain comprises an alpha constant domain comprising at least 95% sequence identity to SEQ ID NO: 9 and   the beta chain further comprises a beta constant domain comprising at least 95% sequence identity to SEQ ID NO: 17.   
     
     
         3 . The method of  claim 1 , wherein
 the alpha constant domain consists of SEQ ID NO: 9, and   the beta constant domain consists of SEQ ID NO: 17.   
     
     
         4 . The method of  claim 2 , wherein
 the alpha constant domain comprises an alpha transmembrane domain VIGFRILLLKVAGFNLLMTL (SEQ ID NO: 18) and   the beta constant domain comprises a beta transmembrane domain TILYEILLGKATLYAVLVSALVL (SEQ ID NO: 19).   
     
     
         5 . The method of  claim 1 , wherein
 the alpha chain comprises an alpha variable domain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 4; and   the beta chain comprises a beta variable domain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 12.   
     
     
         6 . The method of  claim 1 , wherein
 the alpha chain comprises at least 95% sequence identity to SEQ ID NO: 2 and   the beta chain comprises at least 95% sequence identity to SEQ ID NO: 10.   
     
     
         7 . The method of  claim 1 , wherein
 the alpha chain comprising the amino acid sequence of SEQ ID NO: 2 and   the beta chain comprising the amino acid sequence of SEQ ID NO: 10.   
     
     
         8 . The method of  claim 1 , wherein the nucleic acid or nucleic acids encode(s)
 a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 5,   a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 6,   a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 7.   a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 13,   a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 14, and   a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 15.   
     
     
         9 . The method of  claim 1 , wherein the nucleic acid or nucleic acids encode(s)
 a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 5,   a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 6,   a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 7.   a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 13,   a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 14, and   a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 15.   
     
     
         10 . The method of  claim 1 , wherein the nucleic acid or nucleic acids encode(s)
 a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 5,   a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 6,   a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 7.   a CDR1β chain consisting of the amino acid sequences of SEQ ID NO: 13,   a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 14, and   a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 15.   
     
     
         11 . The method of  claim 1 , wherein the nucleic acid or nucleic acids encode(s)
 a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 5,   a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 6,   a CDR3α chain consisting of the amino acid sequence of SEQ ID NO: 7.   a CDR1β chain consisting of the amino acid sequences of SEQ ID NO: 13,   a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 14, and   a CDR3β chain consisting of the amino acid sequence of SEQ ID NO: 15.   
     
     
         12 . The method of  claim 1 , wherein the nucleic acid or nucleic acids encode(s)
 a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 5,   a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 6,   a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 7.   a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 13,   a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 14, and   a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 15.   
     
     
         13 . The method of  claim 1 , wherein the nucleic acid or nucleic acids encode(s)
 a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 5,   a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 6,   a CDR3α chain consisting of the amino acid sequence of SEQ ID NO: 7.   a CDR1β chain consisting of the amino acid sequences of SEQ ID NO: 13,   a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 14, and   a CDR3β chain consisting of the amino acid sequence of SEQ ID NO: 15.   
     
     
         14 . The method of  claim 1 , wherein the nucleic acid or nucleic acids comprises a DNA or an RNA. 
     
     
         15 . The method of  claim 1 , wherein the cancer is colorectal cancer. 
     
     
         16 . The method of  claim 1 , wherein the cancer is glioblastoma. 
     
     
         17 . The method of  claim 1 , wherein the cancer is hepatocellular cancer. 
     
     
         18 . The method of  claim 1 , wherein the cancer is non-small cell lung cancer. 
     
     
         19 . The method of  claim 1 , wherein the cancer is non-Hodgkin's lymphoma. 
     
     
         20 . The method of  claim 1 , wherein the cancer is melanoma.