PROTEIN ANTIGENS AND USES THEREOF
The filed of the present invention relates to immunotherapeutic peptides, peptide binding agents, and their use, for example, in the immunotherapy of cancer.
1 . A method of treating a disease or condition in a subject in need thereof, the method comprising administering to the subject a polypeptide or a polynucleotide encoding the polypeptide, wherein the polypeptide comprises an amino acid sequence comprising at least 8 contiguous amino acids of a viral protein epitope sequence encoded by (I) an E6 gene of Human papillomavirus type 16 (HPV-16) or (II) an E7 gene of HPV-16, wherein:
(a) the subject has been determined to express an MHC encoded by an HLA B07:02 allele and wherein the amino acid sequence is encoded by the E6 gene of HPV-16 and comprises a sequence of RGRWTGRCM (SEQ ID NO: 70);
(b) the subject has been determined to express an MHC encoded by an HLA B08:01 allele and wherein the amino acid sequence is encoded by the E6 gene of HPV-16; or
(c) the subject has been determined to express an MHC encoded by an HLA A24:02 allele and
(i) the amino acid sequence is encoded by the E7 gene of HPV-16 and comprises a sequence of RAHYNIVTF (SEQ ID NO: 83), or
(ii) the amino acid sequence is encoded by the E6 gene of HPV-16 and comprises a sequence of MHQKRTAMF (SEQ ID NO: 66).
2 . The method of claim 1 , wherein the amino acid sequence comprises a first amino acid sequence comprising at least 8 contiguous amino acids of the viral protein epitope sequence encoded by the E6 gene of HPV-16, and a second amino acid sequence comprising at least 8 contiguous amino acids of the viral protein epitope sequence encoded by the E7 gene of HPV-16.
3 . The method of claim 2 , wherein the polypeptide comprises a first polypeptide comprising the first amino acid sequence and a second polypeptide comprising the second amino acid sequence.
4 . The method of claim 1 , wherein the method comprises administering to the subject the polynucleotide encoding the polypeptide, and wherein the polynucleotide is a messenger-RNA (mRNA).
5 . The method of claim 4 , wherein the mRNA is a part of a lipid nanoparticle.
6 . The method of claim 3 , wherein the first polypeptide or the second polypeptide is less than or equal to 600 amino acids in length.
7 . The method of claim 1 , wherein the polypeptide further comprises a modification which increases in vivo half-life, cellular targeting, antigen uptake, antigen processing, MHC affinity, MHC stability, or antigen presentation.
8 . The method of claim 1 , wherein the polypeptide further comprises a poly-glycine or poly-serine linker.
9 . The method of claim 1 , wherein the polypeptide further comprises a peptide sequence of QYIKANSKFIGITE (SEQ ID NO: 1).
10 . The method of claim 1 , wherein the disease or condition is a cancer expressing an antigen encoded by the E6 gene of HPV-16 or the E7 gene of HPV-16.
11 . The method of claim 1 , wherein the disease or condition is a cancer selected from the group consisting of cervical cancer, head and neck cancer, anal cancer, urogenital cancer, and gynecological cancer.
12 . The method of claim 1 , further comprising administering an additional therapeutic agent to the subject, wherein the additional therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, or an immune checkpoint inhibitor.
13 . The method of claim 1 , wherein the subject expresses the MHC encoded by the HLA B07:02 allele.
14 . The method of claim 13 , wherein the amino acid sequence is encoded by the E6 gene of HPV-16 and comprises the sequence of RGRWTGRCM (SEQ ID NO: 70).
15 . The method of claim 1 , wherein the subject expresses the MHC encoded by the HLA B08:01 allele and the amino acid sequence is encoded by the E6 gene of HPV-16.
16 . The method of claim 15 , wherein the amino acid sequence comprises a sequence selected from the group consisting of CVYCKQQLL (SEQ ID NO: 51), DKKQRFHNI (SEQ ID NO: 54), EYRHYCYSL (SEQ ID NO: 55), MHQKRTAMF (SEQ ID NO: 66), SEYRHYCYSL (SEQ ID NO: 73), and SSRTRRETQL (SEQ ID NO: 74).
17 . The method of claim 1 , wherein the subject expresses the MHC encoded by the HLA A24:02 allele, and wherein the amino acid sequence is encoded by the E7 gene of HPV-16 and comprises the sequence of RAHYNIVTF (SEQ ID NO: 83).
18 . The method of claim 1 , wherein the subject expresses the MHC encoded by the HLA A24:02 allele, and wherein the amino acid sequence is encoded by the E6 gene of HPV-16 and comprises the sequence of MHQKRTAMF (SEQ ID NO: 66).
19 . The method of claim 15 , wherein the amino acid sequence comprises a sequence of CVYCKQQLL (SEQ ID NO: 51).
20 . The method of claim 15 , wherein the amino acid sequence comprises a sequence selected from the group consisting of DKKQRFHNI (SEQ ID NO: 54), EYRHYCYSL (SEQ ID NO: 55), MHQKRTAMF (SEQ ID NO: 66), SEYRHYCYSL (SEQ ID NO: 73), and SSRTRRETQL (SEQ ID NO: 74).
21 . The method of claim 1 , wherein the subject is human.