Methods of cancer diagnosis and therapy targeted against the cancer stemline

• US 6,004,528 A
• Filed: 09/18/1997
• Issued: 12/21/1999
• Est. Priority Date: 09/18/1997
• Status: Expired due to Term

• Current Assignee: Ivan Bergstein
• Original Assignee: Ivan Bergstein
• Inventors: Bergstein, Ivan
• Primary Examiner(s): Hutzell, Paula K.
• Assistant Examiner(s): Bansal, Geetha P.
• Application Number:
  US08/933,330
• Time in Patent Office: 824 Days
• Field of Search: 435/7.23, 435/7.9, 435/7.91, 435/7.92, 435/40.5, 435/329, 435/330, 435/332, 435/343, 424/9.6, 424/1.49, 436/501, 436/547, 436/813
• US Class Current: 424/1.49
• CPC Class Codes: G01N 33/5017 for testing neoplastic activity
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: Y10S 436/813 Cancer

Abstract

Improved methods for the diagnosis and treatment of cancer which involve the targeting of slow-growing, relatively mutationally-spared cancer stemline are provided. These methods are an improvement over previous cancer detection and therapeutic methods because they provide for very early cancer detection and treatment and reduce the likelihood of clinical relapse after treatment.

Claims

1. A method for aiding in the diagnosis of cancer in an individual by detecting the presence or absence of a "cancer stem line" (defined as symmetrically dividing stem cells which form increased numbers (relative to normal individual) and/or aggregates of stem cells), the birth of which marks the initiation of cancer, said method comprising the following steps

(i) quantifying in vivo or in vitro the number of stem cells in an individual or tissue sample obtained from an individual and/or detecting the presence or absence of stem cell aggregates in an individual;

(ii) comparing the result of (i) to that of a normal (non-cancerous) individual; and

(iii) positively diagnosing cancer based on either or both (1) an increased number of stem cells relative to a normal individual or (2) the presence of stem cell aggregates or negatively diagnosing cancer based on either or both (1) the lack of a detectable increase in stem cells relative to a normal individual or (2) the absence of stem cell aggregate.

2. The method of claim 1, which is effected using a ligand which specifically binds to a marker expressed by said cancer stem line (of a given blood or tissue type), wherein said marker is a marker also expressed by normal stem cells (of the same blood or tissue type) which comprises the cancer stem line.

3. The method of claim 2, wherein the said ligand is an antibody which specifically binds to a marker expressed by said cancer stem line (of a particular blood or tissue type) wherein said ligand also specifically binds to a marker expressed by normal stem cells (of the same blood or tissue type) which comprise the cancer stem line.

4. The method of claim 3, wherein said ligand is attached directly or indirectly to a detectable label.

5. The method of claim 1, which is effected in vitro or in vivo by assaying for the presence of said cancer stem line in a fluid or solid tissue sample obtained from an individual for whom cancer diagnosis is to be effected.

6. The method of claim 1, wherein said cancer stem line is detected by use of a radioactively or fluorescently labeled ligand which specifically binds to a marker expressed by said cancer stem line (of a particular blood or tissue type), wherein said marker is a marker also expressed by normal stem cells (of the same blood or tissue type), which comprise the cancer stem line.

7. The method of claim 1, wherein said cancer stem line is detected by radionuclide imaging.

8. The method of claim 1, wherein said cancer stem line is detected by flow cytometry or immunohistochemistry.

9. The method of claim 1, wherein said individual does not exhibit any symptoms of cancer.

10. A method for aiding in the diagnosis of cancer comprising the following steps:

(i) assaying for the presence of a cancer stem line (defined as symmetrically dividing stem cells which form increased number and/or aggregates of stem cells, the birth of which marks the initiation of cancer) in a blood or tissue sample obtained from an individual by detecting whether said sample has an increased amount of a marker expressed by normal stem cells relative to a normal (non-cancerous) blood or tissue sample; and

(ii) correlating an increased amount of said marker expressed by normal stem cells to a positive diagnosis for cancer or correlating the absence of an increased amount of said marker to a negative diagnosis for cancer.

11. The method of claim 10, wherein said marker expressed by normal stem cells is detected using a ligand that specifically binds to said marker.

12. The method of claim 11, wherein said ligand is attached to a detectable label.

13. The method of claim 11, wherein said ligand is attached to a radionuclide or fluorescent label.

14. The method of claim 10, which is effected by a technique selected from the group consisting of radionuclide imaging, flow cytometry, and immunohistochemistry.