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 method for designing a cancer vaccine, the method comprising:
(a) identifying one or more novopeptides or one or more nucleic acids encoding novopeptides in a cancerous tissue sample from an individual, wherein the one or more novopeptides comprise a polypeptide between 8 and 40 amino acids in length, wherein the polypeptide comprises a frameshift mutation and induces a protective immune response to cancer, and wherein the polypeptide comprises 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; and
(b) preparing a vaccine comprising one or more polypeptides comprising the one or more novopeptides or one or more nucleic acids encoding the novopeptides.
2. The method of claim 1 , wherein identifying the one or more novopeptides comprises:
(a) obtaining a first nucleic acid sequence from the cancerous tissue sample; and
(b) comparing the first nucleic acid sequence to a second nucleic acid sequence from an individual without cancer or a noncancerous tissue sample from the individual with cancer.
3. The method of claim 2 , wherein the first nucleic acid or the second nucleic acid is a DNA.
4. The method of claim 2 , wherein the first nucleic acid or the second nucleic acid is an RNA.
5. The method of claim 2 , further comprising measuring expression of the one or more novopeptides in the cancerous tissue.
6. The method of claim 2 , wherein the first nucleic acid is obtained from a tumor cell in blood.
7. The method of claim 2 , wherein the second nucleic acid is obtained from blood.
8. The method of claim 2 , wherein the second nucleic acid sequence is obtained from a database of normal sequences.
9. The method of claim 2 , wherein comparing the first nucleic acid sequence to the second nucleic acid sequence detects a mutation comprising an insertion or deletion, a translocation, a single amino acid change, insertion of one or more amino acids, or a frame shift.
10. The method of claim 1 , wherein identifying the one or more novopeptides comprises identifying one or more peptides released from a MEW on a cancerous tissue.
11. The method of claim 1 , further comprising predicting HLA binding for the one or more novopeptides.
12. The method of claim 1 , further comprising predicting an MEW binding strength for the one or more novopeptides.
13. The method of claim 1 , wherein identifying the one or more novopeptides comprises:
(a) obtaining a tumor sample from an individual with cancer;
(b) isolating polypeptides from the tumor sample;
(c) obtaining a sequence of the polypeptides; and
(d) comparing the sequence of the polypeptide to a wild type sequence.
14. The method of claim 1 , wherein the method further comprises screening the one or more novopeptides for eliciting an immune response in a tissue sample obtained from an individual with cancer.
15. The method of claim 14 , wherein screening the one or more novopeptides for eliciting an immune response comprises contacting a tissue sample to the one or more novopeptides and measuring an immune output.
16. The method of claim 15 , wherein the immune output is an antibody response, a T-cell response, or a combination thereof.
17. The method of claim 16 , wherein the antibody response is detected using an ELISA assay, an ELISPOT assay, or an agglutination assay.
18. The method of claim 16 , wherein the T cell response is detected using an cytolytic assay, a 51Cr release assay, a cytokine assay, an ELISPOT assay, an ELISA assay, an intracellular cytokine staining assay, or a MHC tetramer assay.
19. The method of claim 1 , wherein the vaccine comprises a vector.
20. The method of claim 1 , wherein the vaccine comprises an adjuvant.
21. The method of claim 20 , wherein the adjuvant comprises an oil:water emulsion, a GM-CSF, or an interleukin.
22. A method of identifying a tumor specific antigen for use in a cancer vaccine, the method comprising:
isolating a nucleic acid from a tumor cell;
sequencing the nucleic acid from the tumor cell;
identifying an insertion or deletion in the nucleic acid from the tumor cell, thereby identifying a tumor specific antigen; and
preparing a cancer vaccine comprising the identified tumor specific antigen,
wherein the tumor specific antigen comprises 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.
23. The method of claim 22 , wherein the nucleic acid is RNA or DNA.
24. The method of claim 22 , wherein the insertion or deletion results in a frameshift in a gene of the tumor cell.
25. The method of claim 24 , wherein the frameshift in the gene results in a truncated transcript.
26. The method of claim 22 , wherein the tumor specific antigen is a non-oncogene product.