Neoantigens and uses thereof
AssigneeBiontech US Inc.
InventorsVikram Juneja, Zhengxin Dong, Robyn Jessica Eisert
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Abstract
The disclosure herein relates to immunotherapeutic compositions comprising immunotherapeutic peptides comprising neoepitopes. Also disclosed herein are polynucleotides encoding the immunotherapeutic peptides. Also disclosed herein are methods of synthesis of immunotherapeutic peptides comprising neoepitopes and use of the immunotherapeutic compositions including methods of treatment.
Claims55
A pharmaceutical composition comprising:
- (a) at least one polypeptide or a pharmaceutically acceptable salt thereof comprising a first mutant GATA3 peptide sequence and a second mutant GATA3 peptide sequence, wherein
- (i) the first mutant GATA3 peptide sequence and the second mutant GATA3 peptide sequence each comprise at least 8 contiguous amino acids of SEQ ID NO:
- 1, and
- (ii) a C-terminal sequence of the first mutant GATA3 peptide sequence overlaps with an N-terminal sequence of the second mutant GATA3 peptide sequence;
- wherein the at least 8 contiguous amino acids of SEQ ID NO:
- 1 comprises at least one amino acid of sequence PGRPLQTHVL PEPHLALQPLQPHADHAHADAPAIQPVLWTTPPLQHGHRHGLEPCSMLTGPPARVPAVP FDLHFCRSSIMKPKRDGYMFLKAESKIMFAT LQRSSLWCLCSNH (SEQ ID NO:
- 2);
- or
- (b) at least one polynucleotide comprising a sequence encoding the at least one polypeptide.
A pharmaceutical composition comprising:
- one or more mutant GATA3 peptide sequence, the one or more mutant GATA3 peptide sequence comprises a sequence selected from group consisting of ESKIMFATLQRSSL, KPKRDGYMFLKAESKI, SMLTGPPARVPAVPFDLH, EPCSMLTGPPARVPAVPFDLH, LHFCRSSIMKPKRDGYMFLKAESKI, GPPARVPAVPFDLHFCRSSIMKPKRD, and KPKRDGYMFLKAESKIMFATLQRSSLWCLCSNH.
A method of synthesizing a GATA3 peptide, wherein the peptide comprises a sequence of at least two contiguous amino acids selected from the group consisting of Xaa-Cys, Xaa-Ser, and Xaa-Thr, wherein Xaa is any amino acid, the method comprising:
- (a) coupling at least one di-peptide or derivative thereof to an amino acid or derivative thereof of a GATA3 peptide or derivative thereof to obtain a pseudo-proline containing GATA3 peptide or derivative thereof, wherein the di-peptide or derivative thereof comprises a pseudo-proline moiety;
- (b) coupling one or more selected amino acids, small peptides or derivatives thereof to the pseudo-proline containing GATA3 peptide or derivative thereof;
- and
- (c) cleaving the pseudo-proline containing GATA3 peptide or derivative thereof from the resin.
A method of identifying a subject with cancer as a candidate for a therapeutic, the method comprising:
- identifying the subject as one that expresses a protein encoded by an HLA-A02:01 allele, an HLA-A24:02 allele, an HLA-A03:01 allele, an HLA-B07:02 allele and/or an HLA-B08:01 allele, wherein the therapeutic comprises
- (a) at least one polypeptide comprising one or more mutant GATA3 peptide sequences, wherein each of the one or more mutant GATA3 peptide sequences comprises at least one mutant amino acid and is fragment of at least 8 contiguous amino acids of a mutant GATA3 protein arising from a mutation in a GATA3 gene of a cancer cell;
- or
- (b) at least one polynucleotide comprising a sequence encoding the at least one polypeptide, wherein each of the one or more mutant GATA3 peptide sequences or a portion thereof binds to a protein encoded by an HLA-A02:01 allele, an HLA-A24:02 allele, an HLA-A03:01 allele, an HLA-B07:02 allele and/or an HLA-B08:01 allele.
A method of treating a subject with cancer comprising administering to the subject a pharmaceutical composition comprising:
- (a) at least one polypeptide comprising a first mutant GATA3 peptide sequence and a second mutant GATA3 peptide sequence, wherein
- (i) the first mutant GATA3 peptide sequence and the second mutant GATA3 peptide sequence each comprise at least 8 contiguous amino acids of SEQ ID NO:
- 1, and
- (ii) a C-terminal sequence of the first mutant GATA3 peptide sequence overlaps with an N-terminal sequence of the second mutant GATA3 peptide sequence;
- wherein the at least 8 contiguous amino acids of SEQ ID NO:
- 1 comprises at least one amino acid of sequence PGRPLQTHVL PEPHLALQPLQPHADHAHADAPAIQPVLWTTPPLQHGHRHGLEPCSMLTGPPARVPAVP FDLHFCRSSIMKPKRDGYMFLKAESKIMFAT LQRSSLWCLCSNH (SEQ ID NO:
- 2);
- or
- (b) at least one polynucleotide comprising a sequence encoding the at least one polypeptide, wherein HLA alleles expressed by subject are unknown at the time of administering.
Dependencies are inferred from the claim text.