Identification and use of novopeptides for the treatment of cancer
Compositions, methods, systems, apparatus and/or articles of manufacture are disclosed for reducing the susceptibility of a population and/or members thereof to cancer, which may include anti-cancer vaccines, components thereof which may include novopeptides, and methods relating thereto.
1. A vaccine, comprising a continuous amino acid chain, or a continuous portion thereof, according to the formula D1-D2, and an effective amount of an adjuvant, wherein D1 and D2 each comprise a polypeptide sequence encoded by a different exon or continuous portion thereof of a genome, wherein D1 is encoded in a wild type reading frame and D2 is encoded in a non-wild type reading frame and wherein D2 has a sequence selected from: peptide 1-78 (SEQ ID NO: 295), peptide 6-21 (SEQ ID NO:291), peptide RBM (SEQ ID NO: 232), peptide THAP2 (SEQ ID NO: 238), and combinations thereof, wherein the adjuvant is selected from the group consisting of an alum, a CpG, a KLH, an oil emulsion, and combinations thereof.
2. The vaccine of claim 1 , wherein the portion of D1 immediately adjacent to D2 is not a microsatellite or portion thereof.
3. The vaccine of claim 1 , wherein neither of the different exons is an oncogene.
4. The vaccine of claim 1 , wherein a RefSeq of the mammalian species does not contain a continuous nucleic acid sequence encoding the sequence of the continuous amino acid chain.
5. The vaccine of claim 1 , wherein a normal transcriptome of the mammalian species does not contain a continuous nucleic acid sequence encoding the sequence of the continuous amino acid chain.
6. The vaccine of claim 1 , wherein the continuous amino acid chain aligns with at least 90% identity to all or a portion of an mRNA transcript expressed in at least one cancer type of a mammalian species.
7. The vaccine of claim 1 , wherein the continuous amino acid chain has a cancer association ratio of at least 2:1 with respect to at least one cancer type of a mammalian species.
8. The vaccine of claim 1 , wherein the continuous amino acid chain has a cancer serum recognition percentage of at least 40% with respect to at least one cancer type of a mammalian species.
9. The vaccine of claim 1 , wherein the continuous amino acid chain is capable of being displayed in a Class I major histocompatibiity complex (MHC-I) of a type expressed by at least 4 percent of a population.
10. A method comprising administering to a mammal an effective dose of the vaccine of claim 1 .
11. The vaccine of claim 1 wherein the continuous amino acid chain is encoded by a synthetic or recombinant nucleic acid.
12. The vaccine of claim 11 , wherein the continuous amino acid chain comprises a first peptide component displayable in a first MHC type expressed in a first cohort of the population and a second peptide component displayable in a second MHC type expressed in a second cohort of the population, and the first and second cohort together are more numerous by at least 2 percent of the population than either cohort taken separately.
13. A method comprising administering to a mammal by genetic immunization an effective dose of the vaccine of claim 11 .
14. A method comprising administering to a mammal by genetic immunization an effective dose of the vaccine of claim 12 .
15. A method comprising:
(a) administering to a mammal by genetic immunization an effective dose of the vaccine of claim 1 , wherein the continuous amino acid chain is encoded by a synthetic or recombinant nucleic acid, an adjuvant, and a carrier adapted for administration of the vaccine by genetic immunization; and
(b) administering to the mammal an effective dose of the vaccine, in a pharmaceutically acceptable carrier.
16. The method of claim 15 , wherein step (b) is performed at least two weeks after step (a).
17. A vector comprising a promoter and a nucleic acid encoding a continuous amino acid chain, or a continuous portion thereof, according to the formula D1-D2, wherein D1 and D2 each comprise a polypeptide sequence encoded by a different exon or continuous portion thereof of a genome, wherein D1 is encoded in a wild type reading frame and D2 is encoded in a non-wild type reading frame and wherein D2 has a sequence selected from: peptide 1-78 (SEQ ID NO: 295), peptide 6-21 (SEQ ID NO:291), peptide RBM (SEQ ID NO: 232), peptide THAP2 (SEQ ID NO: 238), and combinations thereof.
18. The vaccine of claim 17 , wherein the vector further comprises a nucleic acid encoding an adjuvant selected from a KLH, a GMCSF, an interleukin, and combinations thereof.