USING PHAGE EPITOPES TO PROFILE THE IMMUNE RESPONSE
The present disclosure provides compositions and methods for using one or more polypeptide probes to profile an immune response. The polypeptide probe can be used to detect one or more antibodies from a sample. Furthermore, the present disclosure provides methods and compositions for characterizing a cancer based on the detection of one or more antibodies, such as autoantibodies.
1 . An antibody profiling panel comprising:
a plurality of polypeptide probes, wherein at least one of said polypeptide probes comprises:
a full-length or fragment of a protein listed in Table 1 or polypeptide sequence selected from SEQ ID NO: 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, or 141,
wherein each of said probes in said plurality of polypeptide probes is capable of being specifically bound by an antibody.
2 . The antibody profiling panel of claim 1 , wherein at least one of said polypeptide probes comprises a polypeptide sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, 6, or 7.
3 . The antibody profiling panel of claim 1 , wherein said panel further comprises a full-length or fragment of a protein listed in Tables 2, 3, or 4.
4 . The antibody profiling panel of claim 3 , wherein at least one of said polypeptide probes comprises a polypeptide sequence selected from SEQ ID NO: 8, 9, 10, 11, 12, 13, or 14.
5 . The antibody profiling panel of claim 1 , wherein at least one of said polypeptide probes comprises a full-length or fragment of a protein that is CEP164, RPL34, BRMSL1, NKX3-1, RPSA, Cytochrome C oxidase 5 Subunit, UTR-region of chromosome 11, MAPKKK9, cDNA clone XR — 113641.1, PSA, H2aa4, UBE2I, TIMP2, WDR77, or Deaminase Domain.
6 . The antibody profiling panel of claim 5 , wherein at least one of said polypeptide probe comprises a polypeptide sequence selected from SEQ ID NO: 2, 5, 56, 57, 58, 59, 61, 62, 63, 64, 65, 66, 67, 68, or 69.
7 . The antibody profiling panel of claim 1 , wherein at least one of said polypeptide probes comprise a full-length or fragment of a protein that is FAM53B, 5′UTR BMI1, RP3-323M22, or LOC388789.
8 . The antibody profiling panel of claim 7 , wherein said full-length or fragment of a protein that is FAM53B, 5′UTR BMI1, RP3-323M22, or LOC388789 comprises a polypeptide sequence selected from SEQ ID NO: 9, 11, 14, or 60.
9 . The antibody profiling panel of claim 1 , wherein each of said probes is displayed by a phage.
10 . The antibody profiling panel of claim 1 , wherein each of said probes is attached to a substrate.
11 . The antibody profiling panel of claim 9 , wherein each of said probes is attached to a substrate via said phage.
12 . The antibody profiling panel of claim 10 , wherein said substrate is an array.
13 . The antibody profiling panel of claim 1 , wherein said panel comprises at least 5 polypeptide probes.
14 . The antibody profiling panel of claim 1 , wherein said panel screens a subject for a cancer with greater specificity and sensitivity as compared to a panel with less than said plurality of probes.
15 . The antibody profiling panel of claim 14 , wherein said cancer is prostate, breast or lung cancer.
16 . The antibody profiling panel of claim 1 , wherein said antibody is an autoantibody.
17 . The antibody profiling panel of claim 16 , wherein said autoantibody is a human autoantibody.
18 . A method for screening a subject for a cancer comprising:
detecting in a sample obtained from a subject an expression level of one or more antibodies with at least one polypeptide probe comprising:
a full-length or fragment of a protein listed in Table 1 or
a polypeptide sequence selected from SEQ ID NO: 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, or 141;
wherein said expression level is indicative of the presence, absence, or stage of said cancer.
19 . The method of claim 18 , wherein said screening is with greater specificity and sensitivity as compared to a panel with less than said plurality of probes.
20 . The method of claim 18 , wherein said cancer is prostate, breast or lung cancer.
21 . A method of recommending a biopsy be obtained comprising:
(a) contacting a biological sample obtained from a subject with one or more probes for an antibody, wherein said subject has a PSA level greater than about 2.5 ng/mL;
(b) detecting an expression level of an antibody; and
(c) recommending a biopsy be obtained based on said expression level of said antibody.
22 . The method of claim 21 , wherein said PSA level is between about 2.5 ng/mL and about 10 ng/mL.
23 . The method of claim 21 , further comprising:
(a) contacting a biological sample obtained from said subject with one or more probes for a second antibody when said biopsy provides a positive result for cancer;
(b) detecting an expression level for said second antibody; and
(c) providing a prognosis or theranosis based on said expression level of said second antibody.
24 . A method of screening a subject for a cancer comprising:
(a) contacting a biological sample obtained from said subject with one or more probes for an antibody, wherein said subject has a positive biopsy result for cancer; and
(b) detecting an expression level for said antibody, wherein said expression level is indicative of the presence, absence, or stage of said cancer.
25 . The method of claim 24 , wherein said cancer is aggressive or indolent.
26 . The method of claim 21 or 24 , wherein said detecting is with at least one polypeptide probe comprising:
a full-length or fragment of a protein listed in Table 1, 2, 3, or 4; or
a polypeptide sequence selected from SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, or 141.
27 . The method of claim 21 or 24 , wherein said cancer is prostate cancer, lung cancer or breast cancer.
28 . The method of claim 21 or 24 , further comprising selecting a treatment for said cancer.
29 . The method of claim 21 or 24 , wherein said detecting said expression level is by an immunoassay.
30 . The method of claim 21 or 24 , wherein said subject is a human.
31 . The method of claim 21 or 24 , wherein said antibody is an autoantibody.
32 . The method of claim 31 , wherein said autoantibody is a human autoantibody