Targeting ABCB5 for cancer therapy

• US 9,855,342 B2
• Filed: 01/25/2016
• Issued: 01/02/2018
• Est. Priority Date: 04/12/2007
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Frank, Markus H., Frank, Natasha Y., Sayegh, Mohamed H.
• Primary Examiner(s): Huff, Sheela J.
• Application Number:
  US15/005,364
• Publication Number:
  US 20160136297A1
• Time in Patent Office: 708 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/3513 Protein; Peptide
• CPC Class Codes: C12N 2320/32 Special delivery means, e.g. tissue-specific
• CPC Class Codes: C12Y 302/02022 rRNA N-glycosylase (3.2.2.22)
• CPC Class Codes: G01N 2333/705 Assays involving receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/57492 : involving compounds localized on the membrane of tumor or cancer cells

Abstract

The invention relates to methods for treating a subject by manipulating ABCB5 on a cell as well as related products. The methods include methods of treating cancer using ABCB5 binding molecules such as antibodies and fragments thereof.

Claims

1. A method of delivering a therapeutic agent to an intracellular compartment of a cell, comprising:

contacting a cell with an isolated antibody that selectively binds to ABCB5 conjugated to a therapeutic agent in an effective amount to deliver the therapeutic agent to an intracellular compartment of the cell.

2. A method for determining whether an ABCB5 antigen is present within a sample, comprising:

contacting a sample of a subject with a label-conjugated monoclonal antibody that selectively binds to ABCB5, determining whether an ABCB5 antigen is within the sample by detecting binding of the monoclonal antibody with the ABCB5 antigen.

3. The method of claim 2, wherein the label-conjugated monoclonal antibody is an antibody with a fluorescent probe or a radiological probe.

4. The method of claim 2, wherein the monoclonal antibody has at least one human region.

5. The method of claim 2, wherein the monoclonal antibody competitively inhibits binding of mAb 3C2-1D12 to ABCB5.

6. The method of claim 2, wherein the monoclonal antibody is of immunoglobulin class IgA, IgGb 1, IgG2, IgG3, IgG4 or IgM.

7. The method of claim 2, wherein the monoclonal antibody is a single chain antibody.

8. The method of claim 2, wherein the ABCB5 antigen is on an ABCB5-expressing cell.

9. The method of claim 2, wherein the sample is isolated from a subject and subjected to FACS analysis, Western blotting, or immunohistochemistry.

10. The method of claim 2, wherein the sample is in a subject and the label-conjugated monoclonal antibody is administered to the subject to assess tumor burden, tumor localization or residual tumor mass following chemotherapy or surgical therapy of ABCB5-expressing tumors.

11. A composition, comprising:

a label-conjugated monoclonal antibody that selectively binds to ABCB5, in a carrier.

12. The composition of claim 11, wherein the monoclonal antibody has at least one human region.

13. The composition of claim 11, wherein the monoclonal antibody competitively inhibits binding of mAb 3C2-1D12 to ABCB5.

14. The composition of claim 11, wherein the monoclonal antibody is of immunoglobulin class IgA, IgGb 1, IgG2, IgG3, IgG4 or IgM.

15. The composition of claim 11, wherein the monoclonal antibody is a single chain antibody.

16. The composition of claim 11, wherein the label-conjugated monoclonal antibody is an antibody with a fluorescent probe.

17. The composition of claim 11, wherein the label-conjugated monoclonal antibody is an antibody with a radiological probe.