Methods for detecting and for treating pancreatic cancer

Patent metadata

Field	Value
Publication number	US-12174191-B2
Application number	US-202016928293-A
Country	US
Kind code	B2
Filing date	Jul 14, 2020
Priority date	Jul 22, 2016
Publication date	Dec 24, 2024
Grant date	Dec 24, 2024

Abstract

A method of diagnosing pancreatic cancer in a patient by detecting a level of one or more glycoforms of a Lewis antigen and a level of the one or more glycoforms of MUC5AC. The patient diagnosed with pancreatic cancer then may be treated for this disease. Also, a method for detecting a level of a glycan in a sample which includes using a capture reagent to immobilize the glycan on a substrate; exposing the immobilized glycan to a detection reagent; detecting the level of the immobilized glycan; and combining the biological sample with one or more pre-capture enzymes and/or exposing the immobilized glycan to one or more pre-detection enzymes.

First claim

What is claimed is:

1. A method of diagnosing and treating pancreatic cancer in a subject, said method comprising:
obtaining or having obtained a biological sample from the human subject, wherein said biological sample includes two or more glycoforms of a Lewis A antigen and wherein the two or more glycoforms of the Lewis A antigen are selected from the group consisting of sialyl-Lewis A:sialyl-Lewis A (sLeA:sLeA), sialyl-Lewis A:type1type2 sialyl-N-acetyl-lactosamine (sLeA:sLacNAc t1t2), sialyl-Lewis A:sulfated Lewis A (sLeA:sulfo-LeA), sialyl-Lewis A:sulfated sialyl-Lewis A (sLeA:sulfo-sLeA), sialyl-Lewis A:sulfated Lewis X (sLeA:sulfo-LeX), and sialyl-Lewis A:sulfated sialyl-Lewis X (sLeA:sulfo-sLeX);
detecting or having detected a level of the two or more glycoforms of the Lewis A antigen in the biological sample;
diagnosing the subject with pancreatic cancer when the two or more glycoforms of the Lewis A antigen in the biological sample are elevated as compared to a statistically validated threshold for the two or more glycoforms of the Lewis A antigen; and
administering a therapeutically effective amount of a treatment for pancreatic cancer to the diagnosed subject,
wherein the treatment is surgically resecting a pancreatic cystic lesion in the subject, applying radiation to the pancreatic cystic lesion, or administering a chemotherapeutic agent to the subject.

2. The method of claim 1 , wherein the diagnosis differentiates pancreatic cancer from a benign pancreatic disease.

3. The method of claim 1 , wherein the biological sample further includes one or more glycoforms of MUC5AC;
wherein the detecting step further comprises detecting or having detected a level of the one or more glycoforms of the MUC5AC in the biological sample;
wherein the diagnosing step further comprises diagnosing the subject with pancreatic cancer when two or more glycoforms of the Lewis A antigen and the one or more glycoforms of the MUC5AC in the biological sample are at a different level than a statistically validated threshold for the two or more glycoforms of the Lewis A antigen and the one or more glycoforms of the MUC5AC.

4. The method of claim 1 , wherein the two or more glycoforms of the Lewis A antigen are sLeA:sLeA and sLeA:sLacNAc t1t2.

5. The method of claim 3 , wherein the one or more glycoforms of MUC5AC is selected from the group consisting of MUC5AC:type 1 sialyl-N-acetyl-lactosamine (MUC5AC:sLacNAc t1), MUC5AC:type1type 2 sialyl-N-acetyl-lactosamine (MUC5AC:sLacNAc t1t2), MUC5AC:sialyl-Lewis A (MUC5AC:sLeA), MUC5AC:sialyl-Lewis X (MUC5AC:sLeX), MUC5AC: sulfated-Lewis A (MUC5AC:sulfo-LeA), MUC5AC: sulfated-Lewis X (MUC5AC:sulfo-LeX), MUC5AC:sulfated sialyl-Lewis A (MUC5AC:sulfo-sLeA), and MUC5AC: sulfated sialyl-Lewis X (MUC5AC:sulfo-sLeX).

6. The method of claim 3 , wherein the two or more glycoforms of the Lewis A_antigen are sLeA:sLeA and sLeA:sLacNAc t1t2, and wherein the one or more glycoforms of MUC5AC is MUC5AC:sLacNAc t1t2.

7. The method of claim 3 , wherein the two or more glycoforms of the Lewis A antigen and the one or more glycoforms of MUC5AC are detected with one or more antibodies or glycan-binding proteins.

8. The method of claim 6 , wherein the sLeA:sLeA is detected with a CA19-9 anti-sialyl Lewis A antibody, and wherein the sLeA:sLacNAc t1t2 and the MUC5AC:sLacNAc t1t2 are detected with a TRA-1-60 anti-Lewis antigen antibody.

9. The method of claim 1 , wherein the biological sample is blood serum.

10. The method of claim 3 , wherein the one or more glycoforms of MUC5AC is MUC5AC: sLacNAc t1t2.

11. A method of providing medical services for a human patient suspected of having or having pancreatic cancer, said method comprising:
requesting a biological sample from and diagnostic information about the patient, wherein the diagnostic information is a level of two or more glycoforms of a Lewis A antigen in the biological sample and wherein the two or more glycoforms of the Lewis A antigen are selected from the group consisting of sialyl-Lewis A:sialyl-Lewis A (sLeA:sLeA), sialyl-Lewis A:type1type 2 sialyl-N-acetyl-lactosamine (sLeA:sLacNAc t1t2), sialyl-Lewis A:sulfated Lewis A (sLeA:sulfo-LeA), sialyl-Lewis A:sulfated sialyl-Lewis A (sLeA:sulfo-sLeA), sialyl-Lewis A:sulfated Lewis X (sLeA:sulfo-LeX), and sialyl-Lewis A:sulfated sialyl-Lewis X (sLeA:sulfo-sLeX); and
administering a therapeutically effective amount of a treatment for pancreatic cancer when the diagnostic information indicates that the level of the two or more glycoforms of the Lewis A antigen in the biological sample are at an elevated level as compared to control levels of the two or more glycoforms of the Lewis A antigen,
wherein the treatment is surgically resecting a pancreatic cystic lesion in the subject, applying radiation to the pancreatic cystic lesion, or administering a chemotherapeutic agent to the subject.

12. The method of claim 11 , wherein the diagnostic information differentiates pancreatic cancer from a benign pancreatic disease.

13. The method of claim 11 , wherein the biological sample further includes one or more glycoforms of MUC5AC and the diagnostic information further includes a level of one or more glycoforms of MUC5AC
wherein the administering step further includes administering a therapeutically effective amount of a treatment for pancreatic cancer when the diagnostic information indicates that the level of the two or more glycoforms of the Lewis A antigen and the level of one or more glycoforms of MUC5AC in the biological sample are at an elevated level as compared to the control levels of the two or more glycoforms of the Lewis A antigen and the one or more glycoforms of MUC5AC.

14. The method of claim 13 , wherein the two or more glycoforms of the Lewis A antigen are sLeA:sLeA and sLeA:sLacNAc t1t2 and wherein the one or more glycoforms of MUC5AC is MUC5AC: sLacNAc t1t2.

15. The method of claim 14 , wherein the level of the sLeA:sLeA is detected with a CA19-9 anti-sialyl Lewis A antibody, and wherein the level of the sLeA:sLacNAc t1t2 and the MUC5AC:sLacNAc t1t2 are detected with a TRA-1-60 anti-Lewis antigen antibody.

16. The method of claim 11 , wherein the biological sample is blood serum.

17. The method of claim 13 , wherein the one or more glycoforms of MUC5AC is MUC5AC: sLacNAc t1t2.

18. The method of claim 11 , wherein the two or more glycoforms of the Lewis A antigen are sLeA:sLeA and sLeA:sLacNAc t1t2.

19. The method of claim 13 , wherein the one or more glycoforms of MUC5AC is selected from the group consisting of MUC5AC:type 1 sialyl-N-acetyl-lactosamine (MUC5AC:sLacNAc t1), MUC5AC:type1type 2 sialyl-N-acetyl-lactosamine (MUC5AC: sLacNAc t1t2), MUC5AC: sialyl-Lewis A (MUC5AC:sLeA), MUC5AC:sialyl-Lewis X (MUC5AC:sLeX), MUC5AC:sulfated-Lewis A (MUC5AC: sulfo-LeA), MUC5AC: sulfated-Lewis X (MUC5AC:sulfo-LeX), MUC5AC:sulfated sialyl-Lewis A (MUC5AC:sulfo-sLeA), and MUC5AC:sulfated sialyl-Lewis X (MUC5AC:sulfo-sLeX).

Assignees

• Van Andel Res Institute
• Univ Pittsburgh Commonwealth Sys Higher Education
• Univ Pittsburgh

Inventors

• Haab Brian B
• Brand Randall E

Classifications

• G01N33/57525 Primary

  of the liver or pancreas · CPC title

• G01N2440/38

  addition of carbohydrates, e.g. glycosylation, glycation · CPC title

• G01N2333/91102

  with definite EC number (2.4.1.-) · CPC title

• G01N2333/4725

  Mucins, e.g. human intestinal mucin · CPC title

• C12Y204/01065

  3-Galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase (2.4.1.65), i.e. alpha-1-3 fucosyltransferase · CPC title