CRYPTIC GLYCAN MARKERS AND APPLICATIONS THEREOF

• US 20100178292A1
• Filed: 01/12/2010
• Published: 07/15/2010
• Est. Priority Date: 01/12/2009
• Status: Abandoned Application

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Imperial College London, Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Newsom-Davis, Thomas, Screaton, Gavin, Steinman, Lawrence, Wang, Denong
• Application Number:
  US12/686,102
• Publication Number:
  US 20100178292A1
• Time in Patent Office: Days
• US Class Current: 424/133.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 3/00 Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms preparation by hydrolysis of di-or polysaccharides C13; separation or purification of sucrose, glucose, fructose, lactose or maltose C13
• CPC Class Codes: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/3084 against tumour-associated gangliosides
• CPC Class Codes: C40B 40/12 Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: G01N 2400/12 Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar
• CPC Class Codes: G01N 33/5091 for testing the pathological state of an organism
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells

Abstract

The present invention relates to a novel glycan marker of cancer and monoclonal antibodies against it. Furthermore, novel glycan markers and their use in the detection and monitoring of cancerous cells and cancer-associated or specific antibody signatures are described.

Claims

1. A glyco-epitope that is aberrantly expressed by tumor cells, including human melanoma (Trombelli, MM5), prostate (PC3, DU145, LN-CAP), breast (ZR75.1, MDA-MB 468), and ovarian cancer cell lines (PEA-1, PEO-1, SK-OV-3) and that is displayed by mannose-containing N-glycans of tumor cells and by high-mannose-cluster-carrier protein conjugates in carbohydrate microarrays.

2. An antibody that specifically binds to the glyco-epitope of claim 1.

3. The antibody of claim 2, wherein said antibody is a mouse monoclonal, mouse-human chimeric or humanized antibody, or a functional fragment thereof.

4. The antibody of claim 3, that is an IgM antibody.

5. The antibody of claim 3, that is an IgG antibody.

6. Monoclonal antibody TM10 that specifically binds to the glyco-epitope of claim 1 and that is produced by the hybridoma cell line TM10 and deposited with the ATCC on xx/xx/xxxx.

7. Functional fragments of the monoclonal antibody of claim 6, wherein the binding portion is selected from the group consisting of an Fab, an F(ab'"'"')₂ fragment and an Fv fragment.

8. The antibody of claim 2 wherein the antibody is conjugated to a label that produces a detectable signal.

9. The antibody of claim 8, wherein the label is selected from the group consisting of a radiolabel, an enzyme, a chromophore and a fluorescer.

11. A method to detect cancerous cells or a portion thereof in a biological sample comprising:

providing an antibody or binding portion thereof which recognizes the glyco-epitope of claim 1, wherein the antibody is selected from claim 4, 5, 6 or 7, and wherein the antibody or binding portion thereof is bound to a label that allows detection of said cells.

12. The method of claim 11 wherein the tumor is melanoma.

13. The method of claim 11 wherein the tumor is prostate cancer.

14. The method of claim 11 wherein the tumor is breast cancer.

15. The method of claim 11 wherein the tumor is ovarian cancer.

16. A pharmaceutical composition for vaccinating a mammalian subject against cancer comprising at least one antibody directed against the glyco-epitope of claim 1.

17. The pharmaceutical composition of claim 16, wherein the antibody is selected from claim 4, 5, 6 or 7.

18. A method for inducing a therapeutic immunity by administering the pharmaceutical composition of claim 16 or 17 to a mammalian subject.

10. Hybridoma cell line TM10, as deposited with the ATCC on xx/xx/xxxx.

19. A carbohydrate microarray that displays a multitude of high mannose clusters and that can detect antibodies that specifically bind against these high mannose clusters to detect cancer autoantibody signature profiles so that a sample can be assessed as normal, abnormal or cancerous.

20. A method for detecting cancer autoantibody signature profiles in a biological sample according to claim 19, wherein the antibody is selected from claim 4, 5, 6 or 7.

21. A carbohydrate microarray that displays a multitude of structural and configural variants of synthetic high mannose clusters and that can detect antibodies that specifically bind against these high mannose clusters to detect cancer autoantibody signature profiles so that a sample can be assessed as normal, abnormal or cancerous.

22. A method for detecting cancer autoantibody signature profiles in a sample according to claim 21, wherein the antibody is selected from claim 4, 5, 6 or 7.