Methods and compositions for identifying neoantigens for use in treating and preventing cancer
View Patent ↗Provided herein, are methods of identifying neoantigens for treating and preventing cancer. Also disclosed are methods and compositions for administering identified neoantigens for the treatment and prevention of cancer.
1. A method of measuring antibody binding to a frameshift variant peptide, the method comprising:
(a) contacting a biological sample obtained from a subject to a peptide array comprising a plurality of frameshift variant peptides, wherein the biological sample comprises antibodies, and wherein the plurality of frameshift variant peptides comprise one or more peptides of SEQ ID NO: 22-117 or SEQ ID NO: 128-223, (i) wherein the plurality of frameshift variant peptides comprise peptides encoded by genes having a variant in a microsatellite (MS) in a coding region of the gene; or (ii) wherein the plurality of frameshift variant peptides comprise peptides encoded by a mRNA having an RNA processing error; and
(b) detecting binding of the antibodies within the biological sample to at least one peptide in the peptide array.
2. The method of claim 1 , wherein the plurality of frameshift variant peptides are fixed on a substrate.
3. The method of claim 2 , wherein the substrate comprises glass, composite, resin, or combination thereof.
4. The method of claim 1 , wherein detecting binding comprises at least one of fluorescence, luminescence, calorimetry, chromatography, radioactivity, Bio-Layer Interferometry, and surface plasmon resonance.
5. The method of claim 1 , wherein the peptide array comprises at least about 25,000, about 50,000, about 75,000, about 100,000, about 125,000, about 150,000, about 175,000, about 200,000, about 225,000, about 250,000, about 275,000, about 300,000, about 325,000, about 350,000, about 375,000, or about 400,000 frameshift variant peptides.
6. The method of claim 1 , wherein the biological sample comprises blood, serum, plasma, cerebrospinal fluid, saliva, urine, or combinations thereof.
7. The method of claim 1 , wherein the subject is a mammal.
8. The method of claim 1 , wherein the subject is a human, a dog, a cat, a mouse, a rat, a rabbit, a horse, a cow, or a pig.
9. The method of claim 1 , wherein the subject is suspected of having a cancer.
10. The method of claim 9 , wherein the cancer is selected from the group consisting of acute lymphoblastic leukemia, acute monocytic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, adenocarcinoma, adult T-cell leukemia, astrocytoma, bladder cancer, bone cancer, brain tumor, breast cancer, Burkitt's lymphoma, carcinoma, cervical cancer, chronic lymphocytic leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, endometrial cancer, glioblastoma multiforme, glioma, hepatocellular carcinoma, Hodgkin's lymphoma, inflammatory breast cancer, kidney cancer, leukemia, lung cancer, lymphoma, malignant mesothelioma, medulloblastoma, melanoma, multiple myeloma, neuroblastoma, non-Hodgkin lymphoma, non-small cell lung cancer, ovarian cancer, pancreatic cancer, pituitary tumor, prostate cancer, retinoblastoma, skin cancer, small cell lung cancer, squamous cell carcinoma, stomach cancer, T-cell leukemia, T-cell lymphoma, thyroid cancer, and Wilms' tumor.
11. A method of measuring a level of antibody binding to a neoantigen peptide in a subject, the method comprising:(a) contacting a biological sample obtained from a subject to a peptide array comprising a plurality of frameshift variant peptides, wherein the biological sample comprises antibodies, and wherein the plurality of frameshift variant peptides comprise one or more peptides of SEQ ID NO: 22-117 or SEQ ID NO: 128-223, (i) wherein the plurality of frameshift variant peptides comprise peptides encoded by genes having a variant in a microsatellite (MS) in a coding region of the gene; or (ii) wherein the plurality of frameshift variant peptides comprise peptides encoded by a mRNA having an RNA processing error; and
(b) detecting a level of binding of the antibodies within the biological sample to at least one peptide in the peptide array.
12. The method of claim 11 , wherein the plurality of frameshift variant peptides are fixed on a substrate.
13. The method of claim 12 , wherein the substrate comprises glass, composite, resin, or combination thereof.
14. The method of claim 11 , wherein detecting the level of binding comprises at least one of fluorescence, luminescence, calorimetry, chromatography, radioactivity, Bio-Layer Interferometry, and surface plasmon resonance.
15. The method of claim 11 , wherein the peptide array comprises at least about 25,000, about 50,000, about 75,000, about 100,000, about 125,000, about 150,000, about 175,000, about 200,000, about 225,000, about 250,000, about 275,000, about 300,000, about 325,000, about 350,000, about 375,000, or about 400,000 frameshift variant peptides.
16. The method of claim 11 , wherein the biological sample comprises blood, serum, plasma, cerebrospinal fluid, saliva, urine, or combinations thereof.
17. The method of claim 11 , wherein the subject is a mammal.
18. The method of claim 11 , wherein the subject is a human, a dog, a cat, a mouse, a rat, a rabbit, a horse, a cow, or a pig.
19. The method of claim 11 , wherein the subject is suspected of having a cancer.
20. The method of claim 19 , wherein the cancer is selected from the group consisting of acute lymphoblastic leukemia, acute monocytic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, adenocarcinoma, adult T-cell leukemia, astrocytoma, bladder cancer, bone cancer, brain tumor, breast cancer, Burkitt's lymphoma, carcinoma, cervical cancer, chronic lymphocytic leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, endometrial cancer, glioblastoma multiforme, glioma, hepatocellular carcinoma, Hodgkin's lymphoma, inflammatory breast cancer, kidney cancer, leukemia, lung cancer, lymphoma, malignant mesothelioma, medulloblastoma, melanoma, multiple myeloma, neuroblastoma, non-Hodgkin lymphoma, non-small cell lung cancer, ovarian cancer, pancreatic cancer, pituitary tumor, prostate cancer, retinoblastoma, skin cancer, small cell lung cancer, squamous cell carcinoma, stomach cancer, T-cell leukemia, T-cell lymphoma, thyroid cancer, and Wilms' tumor.
21. The method of claim 11 , wherein the plurality of frameshift variant peptides comprise two or more pooled frameshift peptides.
22. A peptide array comprising a plurality of frameshift variant peptides, wherein the plurality of frameshift variant peptides are fixed on a substrate, wherein the plurality of frameshift variant peptides comprise one or more peptides of SEQ ID NO: 22-117 or SEQ ID NO: 128-223, (i) wherein the plurality of frameshift variant peptides comprise peptides encoded by genes having a variant in a microsatellite (MS) in a coding region of the gene; or (ii) wherein the plurality of frameshift variant peptides comprise peptides encoded by a mRNA having an RNA processing error.
23. The peptide array of claim 22 , wherein the substrate comprises glass, composite, resin, or combination thereof.
24. The peptide array of claim 22 , wherein the peptide array comprises at least about 25,000, about 50,000, about 75,000, about 100,000, about 125,000, about 150,000, about 175,000, about 200,000, about 225,000, about 250,000, about 275,000, about 300,000, about 325,000, about 350,000, about 375,000, or about 400,000 frameshift variant peptides.