COMPOSITIONS AND METHODS FOR DETECTING CANCER
The invention provides sialylated glycans and antibodies that specifically bind to them. The invention's compositions and methods for using them are useful for early detection and diagnosis of cancer.
1 . A method for detecting cancer in a subject, comprising determining, in a biological sample obtained from the subject, the level of one or more compounds selected from the group consisting of
a) Neu5Gc-sialylated antigen,
b) epitope of said Neu5Gc-sialylated antigen,
c) derivative of said Neu5Gc-sialylated antigen, and
d) antibody that specifically binds to one or more of said antigen, said epitope, and said derivative,
wherein the subject is identified as having cancer when a higher level of one or more of said compounds is detected relative to a control normal sample, and the subject is identified as being cancer-free when none of the levels of said compounds is higher than a control normal sample.
2 . The method of claim 1 , wherein said Neu5Gc-sialylated antigen is selected from the group consisting of
i) Neu5Gc-sialylated glycan,
ii) Neu5Gc-sialylated-Le x , and
iii) Neu5Gc-sialylated-Le a .
3 . The method of claim 2 , wherein said Neu5Gc-sialylated glycan is selected from the group consisting of Neu5Gcα2-6GalNAcα-R (Glycan 6), Neu5Gc9Acα2-3Galβ1-4GlcNAcβ-R (Glycan 2), Neu5Gcα2-6Lacβ-R (Glycan 20), and Neu5Gcα2-3Galβ1-3GalNAcβ-R (Glycan 34), Neu5Gcα2-6GalNAcα-OR (Glycan 6), Neu5Gc9Acα2-3Galβ1-4GlcNAcβ-OR (Glycan 2), Neu5Gcα2-6Lacβ-OR (Glycan 20), and Neu5Gcα2-3Galβ1-3GalNAcβ-OR (Glycan 34) wherein R is selected from the group consisting of biotin, albumin, ProNH2, —CH—, —OH, —OCH 3 , —OCH 2 —CH 3 , —H, hydrido, hydroxy, alkoxyl, oxygen, carbon, sulfur, nitrogen, phosphorus, NH 2 , ProNH 2 ═O(CH 2 ) 2 CH 2 NH 2 , (OCH 2 CH 2 ) 6 NH 2 , O(CH 2 ) 3 NHCOCH 2 (OCH 2 CH 2 ) 6 NH 2 , the fluorescent labels 2-aminobenzamide (AB) and/or 2-aminobenzoid acid (AA), 2-aminobenzamide analog that contains an alkyl amine (AEAB), aminooxy-groups, methylaminooxy-groups, hydrazide groups, amino lipid 1,2-dihexadecyl-sn-glycero-3-phosphoethanolamine (DHPE), aminooxy (AO) functionalized DHPE, glycosylphosphatidylinositol (GPI), and wherein Lac is Galβ1-4GlcNAc.
4 . The method of claim 3 , wherein said Neu5Gc-sialylated glycan comprises Neu5Gcα2-6GalNAcα-R (Glycan 6).
5 . The method of claim 2 , wherein said Neu5Gc-sialylated-Le x comprises Neu5Gcα2-3Galβ1-4(Fucα1-3)GlcNAc).
6 . The method of claim 2 , wherein said Neu5Gc-sialylated-Le a comprises one or more of (Neu5Gcα2-3Galβ1-3(Fucα1-4)GlcNAc and 9-O-acetyl-GD3 (Neu5,9Ac 2 α2-8Neu5Acα2-3Galβ1-4Glcβ1-1Ceramide).
7 . The method of claim 1 , wherein said antibody specifically binds to a Neu5Gc-sialylated glycan that comprises Neu5Gcα2-6GalNAcα-R (Glycan 6).
8 . The method of claim 1 , wherein said determining comprises detecting antibody that specifically binds to one or more of said Neu5Gc-sialylated antigen, said epitope of said antigen, and said derivative of said antigen.
9 . The method of claim 1 , wherein said subject is indicated for initiation of anti-cancer therapy when an increase in the level of one or more of said compounds is detected.
10 . The method of claim 1 , wherein said subject is indicated for confirmatory diagnostic cancer testing an increase in the level of one or more of said compounds is detected.
11 . The method of claim 1 , further comprising initiating anti-cancer therapy in a subject having an increase in the level of one or more of said compounds.
12 . The method of claim 1 , further comprising performing a confirmatory diagnostic cancer test in a subject having an increase in the level of one or more of said compounds.
13 . The method of claim 8 , wherein said antibody specifically binds to a Neu5Gc-sialylated glycan that comprises Neu5Gcα2-6GalNAcα-R (Glycan 6).
14 . The method of claim 8 , wherein said antibody has an area under the curve (AUC) for a Receiver Operator Characteristic (ROC) curve of cancer of greater than 0.50.
15 . The method of claim 8 , wherein said antibody has a cancer specificity greater than 50%.
16 . The method of claim 8 , wherein said antibody has a cancer sensitivity greater than 50%.
17 . An isolated Neu5Gc-sialylated antigen selected from the group consisting of
i) Neu5Gc-sialylated glycan,
ii) Neu5Gc-sialylated-Le x , and
iii) Neu5Gc-sialylated-Le a .
18 . An antibody that specifically binds to one or more Neu5Gc-sialylated antigen of claim 17 .
19 . An antibody that specifically binds to one or more antibody of claim 18 .
20 . A kit comprising a composition that contains one or more of the Neu5Gc-sialylated antigen of claim 17 , the antibody of claim 18 , and the antibody of claim 19 .