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 . (canceled)
2 . 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 a mutation 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.
3 . The method of claim 1 , wherein the mutation comprises a point mutation, frame shift mutation, in-frame insertion or deletion, translocation, improper splicing, post-transcriptional event, variation, or other alteration in a nucleic acid sequence from a non-cancerous reference sequence.
4 . The method of claim 1 , wherein the tumor specific antigen comprises an amino acid sequence as set forth in SEQ ID NO: 293, SEQ ID NO: 290, SEQ ID NO: 296, SEQ ID NO: 234, SEQ ID NO: 240, or a combination thereof.
5 . The method of claim 1 , wherein the nucleic acid is RNA or DNA.
6 . The method of claim 1 , wherein the insertion or deletion results in a frameshift in a gene of the tumor cell.
7 . The method of claim 6 , wherein the frameshift in the gene results in a truncated transcript.
8 . The method of claim 1 , wherein the tumor specific antigen is a non-oncogene product.
9 . A vaccine comprising:
a continuous amino acid chain, or a portion thereof, from 8 to 40 amino acids in length, according to the formula D1-D2, and
an effective amount of an adjuvant,
wherein D1 and D2 each have at least 90% sequence identity to a polypeptide sequence encoded by a different exon or continuous portion thereof of a genome of a mammalian species, wherein D1 is encoded in a wild type reading frame and D2 is encoded in a non-wild type reading frame.
10 . The vaccine of claim 9 , wherein D2 has an amino acid sequence as set forth in SEQ ID NO: 293, SEQ ID NO: 290, SEQ ID NO: 296, SEQ ID NO: 234, SEQ ID NO: 240, or a combination thereof.
11 . The vaccine of claim 9 , wherein the adjuvant is an alum, a CpG, a KLH, an oil emulsion, or a combination thereof.
12 . The vaccine of claim 9 , 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.
13 . The vaccine of claim 9 , 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.
14 . A vector comprising:
a promoter and a nucleic acid encoding a continuous amino acid chain, or a portion thereof, from 8 to 40 amino acids in length, according to the formula D1-D2,
wherein D1 and D2 each have at least 90% sequence identity to a polypeptide sequence encoded by a different exon or continuous portion thereof of a genome of a mammalian species, wherein D1 is encoded in a wild type reading frame and D2 is encoded in a non-wild type reading frame.
15 . The vector of claim 14 , wherein D2 has an amino acid sequence as set forth in SEQ ID NO: 293, SEQ ID NO: 290, SEQ ID NO: 296, SEQ ID NO: 234, SEQ ID NO: 240, or a combination thereof.
16 . The vector of claim 14 , wherein the vector further comprises a nucleic acid encoding an adjuvant comprising a KLH, a GMCSF, an interleukin, or a combination thereof.
17 . 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
(b) preparing a vaccine comprising one or more polypeptides comprising the one or more novopeptides or one or more nucleic acids encoding the novopeptides.
18 . The method of claim 17 , wherein the polypeptide comprises an amino acid sequence as set forth in SEQ ID NO: 293, SEQ ID NO: 290, SEQ ID NO: 296, SEQ ID NO: 234, SEQ ID NO: 240, or a combination thereof.
19 . The method of claim 17 , 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.
20 . The method of claim 19 , wherein the first nucleic acid or the second nucleic acid is a DNA or an RNA.
21 . The method of claim 17 , 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.