Neoantigens and uses thereof
AssigneeBiontech US Inc.
InventorVikram Juneja
Life of this patent
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Abstract
Disclosed herein relates to immunotherapeutic compositions comprising immunotherapeutic peptides comprising neoepitopes, polynucleotides encoding the immunotherapeutic peptides, antigen presenting cells comprising the immunotherapeutic peptides or polynucleotides, or T cell receptors specific for the neoepitopes. Also disclosed herein is use of the immunotherapeutic compositions.
Claims96
A composition comprising:
- (a) at least one polypeptide or a pharmaceutically acceptable salt thereof comprising two or more mutant RAS peptide sequences selected from the group consisting of;
- (i) KLVVVGADGV, KLVVVGACGV, KLVVVGAVGV, LVVVGADGV, LVVVGACGV, LVVVGAVGV;
- (ii) GADGVGKSAL, GACGVGKSAL, GAVGVGKSAL, GADGVGKSA, GACGVGKSA, GAVGVGKSA;
- and/or
- (iii) VVGADGVGK, VVGACGVGK, VVGAVGVGK, VVVGADGVGK, VVVGACGVGK, VVVGAVGVGK;
- or
- (b) at least one polynucleotide encoding the at least one polypeptide.
A composition comprising:
- (a) at least one polypeptide or a pharmaceutically acceptable salt thereof comprising two or more mutant RAS peptide sequences each comprising:
- (i) at least 8 contiguous amino acids of a mutant RAS protein comprising a mutation at G12, and
- (ii) the mutation at G12;
- and
- further wherein three or more amino acid residues that are heterologous to the mutant RAS protein are linked to the N-terminus or C-terminus of the two or more mutant RAS peptide sequences, wherein the three or more amino acid residues enhance processing of the mutant RAS peptide sequences in cell and/or enhance presentation of an epitope of the mutant RAS peptide sequences;
- or
- (b) at least one polynucleotide encoding the at least one polypeptide.
A composition comprising
- (a) at least one polypeptide or a pharmaceutically acceptable salt thereof of the formula (XaaN)N-(XaaRAS)P-(XaaC)C
- wherein
- P is an integer greater than 7;
- (XaaRAS)P is a mutant RAS peptide sequence comprising at least 8 contiguous amino acids of a mutant RAS protein;
- the at least 8 contiguous amino acids comprising at least 8 contiguous amino acids of the sequence
- Lys1 Leu2 Val3 Val4 Val5 Gly6 Ala7 Xaa8 Gly9 Val10 Gly11 Lys12 Ser13 Ala14Leu15
- N is (i) 0 or (ii) an integer greater than 2;
- (XaaN)N is any amino acid sequence heterologous to the mutant RAS protein;
- C is (i) 0 or (ii) an integer greater than 2;
- (XaaC)C is any amino acid sequence heterologous to the mutant RAS protein;
- Xaa8 is selected from the group consisting of Asp, Val, Cys, Ala, Arg and Ser;
- the polypeptide is not KLVVVGAVGVGKSALTIQL;
- and
- wherein if N is 0 C is not 0 and if C is 0 N is not 0;
- or
- (b) at least one polynucleotide encoding the at least one polypeptide.
A composition comprising
- (a) at least one polypeptide or a pharmaceutically acceptable salt thereof comprising of an amino acid sequence of
- Xaa1-Xaa2-Val3-Val4-Val5-Gly6-Ala7-Xaa8-Gly9-Xaa10
- wherein
- Xaa1 is not Ala;
- with the proviso that when Xaa1 is not Lys, Xaa2 is Leu and/or Xaa10 is Gly;
- Xaa2 is not Glu;
- with the proviso that when Xaa2 is not Leu, Xaa1 is Lys and/or Xaa10 is Gly;
- Xaa8 is selected from the group consisting of Asp, Val, Cys, Ala, Arg and Ser;
- with the proviso that when Xaa8 is Glu, Xaa1 is not Tyr and/or Xaa2 is not Leu, and
- with the proviso that when Xaa8 is Val, Xaa1 is not Lys;
- Xaa10 is any amino acid;
- with the proviso that when Xaa10 is not Gly, Xaa1 is Lys and/or Xaa2 is Leu;
- and
- the polypeptide comprises an HLA-A02:01-restricted T cell epitope, HLA-A03:01-restricted T cell epitope, an HLA-A11:01-restricted T cell epitope, an HLA-A03:02-restricted T cell epitope, an HLA-A30:01-restricted T cell epitope, an HLA-A31:01-restricted T cell epitope, an HLA-A33:01-restricted T cell epitope, an HLA-A33:03-restricted T cell epitope, an HLA-A68:01-restricted T cell epitope, or an HLA-A74:01-restricted T cell epitope that binds to an HLA-A02:01, HLA-A03:01, HLA-A11:01, HLA-A03:02, HLA-A30:01, HLA-A31:01, HLA-A33:01, HLA-A33:03, HLA-A68:01, and/or an HLA-A74:01 molecule;
- and
- induces an HLA-A02:01-restricted cytotoxic T cell response, an HLA-A02:01-restricted cytotoxic T cell response, HLA-A03:01-restricted cytotoxic T cell response, an HLA-A11:01-restricted cytotoxic T cell response, an HLA-A03:02-restricted cytotoxic T cell response, an HLA-A30:01-restricted cytotoxic T cell response, an HLA-A31:01-restricted cytotoxic T cell response, an HLA-A33:01-restricted cytotoxic T cell response, an HLA-A33:03-restricted cytotoxic T cell response, an HLA-A68:01-restricted cytotoxic T cell response, or an HLA-A74:01-restricted cytotoxic T cell response;
- and
- that binds to an HLA-A02:01, HLA-A03:01, HLA-A11:01, HLA-A03:02, HLA-A30:01, HLA-A31:01, HLA-A33:01, HLA-A33:03, HLA-A68:01, and/or an HLA-A74:01;
- or
- (b) at least one polynucleotide encoding the at least one polypeptide.
A composition comprising:
- (a) at least one polypeptide or a pharmaceutically acceptable salt thereof comprising one or more mutant RAS peptide sequences each comprising:
- (i) at least 8 contiguous amino acids of a mutant RAS protein comprising a G12A, G12C, G12D, G12R, G12S, or G12V mutation, and
- (ii) the G12A, G12C, G12D, G12R, G12S, or G12V mutation;
- and
- further wherein the peptide:
- (i) comprises a mutation not encoded by a genome of a cancer cell and has an affinity or predicted affinity of 150 nM or less for an HLA-A02:01 allele and/or a half-life of 2 hours or more, or
- (j) has a half life of 2 hours or more and an affinity or predicted affinity of 150 nM or less for an HLA-A02:01 allele, an HLA-A03:01 allele, an HLA-A11:01 allele, an HLA-A03:02 allele, an HLA-A30:01 allele, an HLA-A31:01 allele, an HLA-A33:01 allele, an HLA-A33:03 allele, an HLA-A68:01 allele, or an HLA-A74:01 allele and/or an HLA-008:02 allele;
- or
- (b) at least one polynucleotide encoding the at least one polypeptide.
A composition comprising:
- (a) at least one polypeptide or a pharmaceutically acceptable salt thereof comprising one or more mutant RAS peptide sequences selected from the group consisting of:
- DTAGHEEY, TAGHEEYSAM, DILDTAGHE, DILDTAGH, ILDTAGHEE, ILDTAGHE, DILDTAGHEEY, DTAGHEEYS, LLDILDTAGH, DILDTAGRE, DILDTAGR, ILDTAGREE, ILDTAGRE, CLLDILDTAGR, TAGREEYSAM, REEYSAMRD, DTAGKEEYSAM, CLLDILDTAGK, DTAGKEEY, LLDILDTAGK, ILDTAGKE, ILDTAGKEE, DTAGLEEY, ILDTAGLE, DILDTAGL, ILDTAGLEE, GLEEYSAMRDQY, LLDILDTAGLE, LDILDTAGL, DILDTAGLE, DILDTAGLEEY, AGVGKSAL, GAAGVGKSAL, AAGVGKSAL, CGVGKSAL, ACGVGKSAL, DGVGKSAL, ADGVGKSAL, DGVGKSALTI, GARGVGKSA, KLVVVGARGV, VVVGARGV, SGVGKSAL, VVVGASGVGK, GASGVGKSAL, VGVGKSAL, VVVGAGCVGK, KLVVVGAGC, GDVGKSAL, DVGKSALTI, VVVGAGDVGK, TAGKEEYSAM, DTAGHEEYSAM, TAGHEEYSA, DTAGREEYSAM, TAGKEEYSA, AAGVGKSA, AGCVGKSAL, AGDVGKSAL, AGKEEYSAMR, AGVGKSALTI, ARGVGKSAL, ASGVGKSA, ASGVGKSAL, AVGVGKSA, CVGKSALTI, DILDTAGK, DILDTAGREEY, DTAGHEEYSAMR, DTAGKEEYS, DTAGKEEYSAMR, DTAGLEEYS, DTAGLEEYSA, DTAGLEEYSAMR, DTAGREEYS, DTAGREEYSAMR, GAAGVGKSA, GACGVGKSA, GACGVGKSAL, GADGVGKS, GAGDVGKSA, GAGDVGKSAL, GASGVGKSA, GCVGKSAL, GCVGKSALTI, GHEEYSAM, GKEEYSAM, GLEEYSAMR, GREEYSAM, GREEYSAMR, HEEYSAMRD, KEEYSAMRD, KLVVVGASG, LDILDTAGR, LEEYSAMRD, LVVVGARGV, LVVVGASGV, REEYSAMRDQY, RGVGKSAL, TAGLEEYSA, TEYKLVVVGAA, VGAAGVGKSA, VGADGVGK, VGASGVGKSA, VGVGKSALTI, VVVGAAGV, VVVGAVGV, YKLVVVGAC, YKLVVVGAD, YKLVVVGAR, and DILDTAGKE;
- or
- (b) at least one polynucleotide encoding the at least one polypeptide.
A method of treating a subject with cancer comprising administering to the subject a peptide with a sequence of VVGADGVGK, VVGACGVGK, VVGAVGVGK, VVVGADGVGK, VVVGACGVGK, VVVGAVGVGK, wherein the subject expresses a protein encoded by an HLA-A02:01 allele, an HLA-A03:01 allele, an HLA-A11:01 allele, an HLA-A03:02 allele, an HLA-A30:01 allele, an HLA-A31:01 allele, an HLA-A33:01 allele, an HLA-A33:03 allele, an HLA-A68:01 allele, an HLA-A74:01 allele, or an HLA-008:02 allele of the subject's genome.
A method of treating a subject with cancer comprising administering to the subject a mutant RAS peptide or a nucleic acid encoding the mutant RAS peptide, wherein the mutant RAS peptide comprises at least 8 contiguous amino acids of a mutant RAS protein comprising a mutation at G12, wherein the peptide comprises the mutation at G12 and binds to HLA-A11:01 or HLA-A03:01, wherein the subject is identified as expressing a protein encoded by an HLA-A03:01 allele, an HLA-A11:01 allele, an HLA-A03:02 allele, an HLA-A30:01 allele, an HLA-A31:01 allele, an HLA-A33:01 allele, an HLA-A33:03 allele, an HLA-A68:01 allele, or an HLA-A74:01 allele.
A method of treating a subject with cancer comprising administering to the subject a peptide comprising a sequence GADGVGKSAL, GACGVGKSAL, GAVGVGKSAL, GADGVGKSA, GACGVGKSA, or GAVGVGKSA;
- wherein the subject expresses a protein encoded by an HLA-A02:01 allele, an HLA-A03:01 allele, an HLA-A11:01 allele, an HLA-A03:02 allele, an HLA-A30:01 allele, an HLA-A31:01 allele, an HLA-A33:01 allele, an HLA-A33:03 allele, an HLA-A68:01 allele, an HLA-A74:01 allele, or an HLA-008:02 allele of the subject's genome that binds to the peptide.
A method of treating a subject with cancer comprising administering to the subject a first and a second peptide or a nucleic acid encoding the first and second peptide, wherein the first and second peptides comprise at least two of:
- (1) KLVVVGADGV, KLVVVGACGV, KLVVVGAVGV, LVVVGADGV, LVVVGACGV, LVVVGAVGV;
- (2) GADGVGKSAL, GACGVGKSAL, GAVGVGKSAL, GADGVGKSA, GACGVGKSA, GAVGVGKSA;
- and (3) VVGADGVGK, VVGACGVGK, VVGAVGVGK, VVVGADGVGK, VVVGACGVGK, VVVGAVGVGK;
- wherein the subject's HLA allele expression is unknown at the time of administration.
A method of treating a subject with cancer comprising administering to the subject a mutant RAS peptide or a nucleic acid encoding the mutant RAS peptide, wherein the mutant RAS peptide comprises at least 8 contiguous amino acids of a mutant RAS protein comprising a G12C mutation, wherein the peptide comprises the G12C mutation, and further wherein the peptide comprises a stabilizing mutation not encoded by a genome of a cancer cell, wherein the subject expresses a protein encoded by an HLA-A02:01 allele, an HLA-A03:01 allele, an HLA-A11:01 allele, an HLA-A03:02 allele, an HLA-A30:01 allele, an HLA-A31:01 allele, an HLA-A33:01 allele, an HLA-A33:03 allele, an HLA-A68:01 allele, an HLA-A74:01 allele, or an HLA-008:02 allele.
A method of identifying a subject with cancer as a candidate for a therapeutic, the method comprising identifying the subject as a subject that expresses a protein encoded by an HLA-A03:01 allele, an HLA-A11:01 allele, an HLA-A03:02 allele, an HLA-A30:01 allele, an HLA-A31:01 allele, an HLA-A33:01 allele, an HLA-A33:03 allele, an HLA-A68:01 allele, or an HLA-A74:01 allele, wherein the therapeutic is a mutant RAS peptide or a nucleic acid encoding the mutant RAS peptide, wherein the mutant RAS peptide comprises at least 8 contiguous amino acids of a mutant RAS protein comprising a mutation at G12, wherein the peptide comprises the mutation at G12 and binds to a protein encoded by an HLA-A03:01 allele, an HLA-A11:01 allele, an HLA-A03:02 allele, an HLA-A30:01 allele, an HLA-A31:01 allele, an HLA-A33:01 allele, an HLA-A33:03 allele, an HLA-A68:01 allele, or an HLA-A74:01 allele.
A method of treating a subject with cancer, the method comprising:
- (a) identifying a first protein expressed by the subject, wherein the first protein is encoded by a first HLA allele of the subject and wherein the first HLA allele is an HLA allele provided in any one of Tables 1 to 14;
- and
- (b) administering to the subject (i) a first mutant RAS peptide, wherein the first mutant RAS peptide is a peptide to the first HLA allele provided in any one of Tables 1 to 14, or (ii) a polynucleic acid encoding the first mutant RAS peptide.
Dependencies are inferred from the claim text.