Shared neoantigens

Abstract

Disclosed herein in one aspect is a pharmaceutical composition comprising a plurality of neoantigenic peptides and a pharmaceutically acceptable carrier, each neoantigenic peptide comprising a tumor-specific neoepitope capable of binding to an HLA protein in a subject, each tumor-specific neoepitope comprising a tumor-specific mutation present in a tumor, wherein (a) the composition comprises neoantigenic peptides comprising tumor-specific mutations present in at least 1% of subjects in a population of subjects suffering from cancer; (b) the composition comprises neoantigenic peptides comprising tumor-specific neoepitopes which bind to HLA proteins present in at least 5% of subjects in the population; and (c) the composition comprises at least one neoantigenic peptide capable of eliciting an immune response against a tumor present in at least 5% of the subjects in the population of subjects suffering from cancer.

1 .- 93 . (canceled) 
     
     
         94 . A pharmaceutical composition comprising
 (i) a polypeptide comprising at least one amino acid sequence comprising at least 8 amino contiguous acids of:   
       
         
           
                 
               
                   (SEQ ID NO: 1297) 
                 
                   FSHSSHMLTTPTPMHPPSSLSFGPHPPLQHGHRHGLEPCSMLTGPPARVP 
                 
                     
                 
                   AVPFDLHFCRSSIMKPKRDGYMFLKAESKIMFATLQRSSLWCLCSNH, 
                 
             
                
                
                
                
               
            
           
         
         (ii) a nucleic acid encoding the polypeptide, 
         (iii) antigen presenting cells (APCs) comprising (i) or (ii), or 
         (iv) T cells stimulated with APCs comprising (i) or (ii); and 
         a pharmaceutically acceptable carrier. 
       
     
     
         95 . The pharmaceutical composition of  claim 94 , wherein the at least one amino acid sequence binds to a protein encoded by an HLA allele. 
     
     
         96 . The pharmaceutical composition of  claim 95 , wherein the at least one amino acid sequence binds to a protein encoded by an HLA-A, HLA-B or HLA-C allele with a K D  of less than 500 nM. 
     
     
         97 . The pharmaceutical composition of  claim 95 , wherein the at least one amino acid sequence binds to a protein encoded by a class II HLA allele with a binding affinity of less than 1000 nM. 
     
     
         98 . The pharmaceutical composition of  claim 94 , wherein the polypeptide is from 8 to 50 amino acids in length. 
     
     
         99 . The pharmaceutical composition of  claim 94 , wherein the at least one amino acid sequence comprises at least 8 amino contiguous acids of: 
       
         
           
                 
               
                   (residues 26-97 of SEQ ID NO: 1297) 
                 
                   PPLQHGHRHGLEPCSMLTGPPARVPAVPFDLHFCRSSIMKPKRDGYMFLK 
                 
                     
                 
                   AESKIMFATLQRSSLWCLCSNH. 
                 
             
                
                
                
                
               
            
           
         
       
     
     
         100 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence ESKIMFATL (SEQ ID NOs: 13457, 13526, 13595, 13661, 13717, 13772, 33585). 
     
     
         101 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence FATLQRSSL (SEQ ID NOs: 13454, 13523, 13592, 13658, 13714, 13769, 33527). 
     
     
         102 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence FLKAESKIM (SEQ ID NOs: 13438, 13507, 13576, 13643, 13700, 13754, 33542). 
     
     
         103 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence FLKAESKIMF (SEQ ID NOs: 13488, 13559, 13628, 13687, 13741, 13796). 
     
     
         104 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence GPPARVPAV (SEQ ID NOs: 13452, 13521, 13590, 13656, 13712, 13767, 33554). 
     
     
         105 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence IMKPKRDGYM (SEQ ID NOs: 13477, 13548, 13617, 13679, 13734, 13789). 
     
     
         106 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence KIMFATLQR (SEQ ID NOs: 13441, 13510, 13579, 13646, 13703, 13757, 33513). 
     
     
         107 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence KPKRDGYMF (SEQ ID NOs: 13453, 13522, 13591, 13657, 13713, 13768, 33555). 
     
     
         108 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence KPKRDGYMFL (SEQ ID NOs: 13485, 13556, 13625, 13684, 13738, 13793, 33556). 
     
     
         109 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence LHFCRSSIM (SEQ ID NOs: 13456, 13525, 13594, 13660, 13716, 13771). 
     
     
         110 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence MFATLQRSSL (SEQ ID NOs: 13487, 13558, 13627, 13686, 13740, 13795). 
     
     
         111 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence MFLKAESKI (SEQ ID NOs: 13444, 13513, 13582, 13649, 13706, 13760, 33726). 
     
     
         112 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence MLTGPPARV (SEQ ID NOs: 13437, 13506, 13575, 13642, 13699, 13753, 33517). 
     
     
         113 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence QPVLWTTPPL (SEQ ID NOs: 13484, 13555, 13624, 33599). 
     
     
         114 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence SMLTGPPARV (SEQ ID NOs: 13471, 13541, 13610, 13672, 13728, 13783, 33521). 
     
     
         115 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence TLQRSSLWCL (SEQ ID NOs: 13473, 13543, 13612, 13674, 13730, 13785, 33523). 
     
     
         116 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence VLPEPHLAL (SEQ ID NOs: 13434). 
     
     
         117 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence: YMFLKAESK (SEQ ID NOs: 13440, 13509, 13578, 13645, 13702, 13756, 33520). 
     
     
         118 . The pharmaceutical composition of  claim 94 , wherein the polypeptide comprises an amino acid sequence YMFLKAESKI (SEQ ID NOs: 13472, 13542, 13611, 13673, 13729, 13784, 33522). 
     
     
         119 . The pharmaceutical composition of  claim 94 , wherein the pharmaceutical composition comprises (iv). 
     
     
         120 . The pharmaceutical composition of  claim 94 , wherein the pharmaceutical composition comprises (i) or (ii). 
     
     
         121 . The pharmaceutical composition of  claim 94 , further comprising an adjuvant or an immunomodulator. 
     
     
         122 . The pharmaceutical composition of  claim 121 , wherein the immunomodulator or adjuvant is poly(I:C). 
     
     
         123 . The pharmaceutical composition of  claim 94 , wherein the pharmaceutical composition is an immunogenic composition or a vaccine composition.