Targeting ABCB5 for cancer therapy

• US 8,697,072 B2
• Filed: 03/10/2011
• Issued: 04/15/2014
• 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:
  US13/044,854
• Publication Number:
  US 20110165149A1
• Time in Patent Office: 1,132 Days
• Field of Search: None
• US Class Current: 424/133.1
• 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 related 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 or peptide 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. The method of claim 1, wherein the isolated peptide is an antibody or antigen binding fragment thereof.

3. The method of claim 1, wherein the therapeutic agent is a toxin.

4. The method of claim 1, wherein the therapeutic agent is an siRNA.

5. The method of claim 1, wherein the therapeutic agent is a chemotherapeutic agent.

6. The method of claim 1, wherein the therapeutic agent is a therapeutic antibody.

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

contacting a cell with an isolated antibody or peptide 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, further comprising contacting a cell with an isolated molecule that selectively binds to a surface marker selected from the group consisting of 25 CD49e, CD133, and CD166.

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

contacting a cell with an isolated antibody or peptide 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, further comprising contacting a cell with an isolated molecule that selectively binds to a surface marker selected from the group consisting of BMPR1a, TIE-1, VE-cadherin (CD144) and nestin.

9. A method for treating a subject, comprising

systemically administering an isolated peptide that selectively binds to ABCB5 and comprises an amino acid sequence having SEQ ID NO:

1 (heavy chain variable region) and SEQ ID NO;

2 (light chain variable region) or having the following 6 CDRs;

SEQ ID NO;

3 (CDR-H1), SEQ ID NO;

4 (CDR-H2), SEQ ID NO;

5 (CDR-H3), SEQ ID NO;

6 (CDR-L1), SEQ ID NO;

7 (CDR-L2), or SEQ ID NO;

8 (CDR-L3), to a subject having cancer in an effective amount to treat the cancer.

10. A method for treating a subject, comprising

administering a composition comprising an isolated peptide having 6 CDRs that selectively bind to ABCB5 wherein the isolated peptide comprises SEQ ID NO:

1 (heavy chain variable region) and SEQ ID NO;

2 (light chain variable region) or has the following 6 CDRs;

SEQ ID NO;

3 (CDR-H1), SEQ ID NO;

4 (CDR-H2), SEQ ID NO;

5 (CDR-H3), SEQ ID NO;

6 (CDR-L1), SEQ ID NO;

7 (CDR-L2), or SEQ ID NO;

8 (CDR-L3), wherein the isolated peptide is not mAb 3C2-1D12 to a subject having cancer in an effective amount to treat the cancer.

11. A method for treating a subject, comprising

administering an isolated peptide that selectively binds to ABCB5 and comprises an amino acid sequence having 6 CDRs wherein the isolated peptide comprises SEQ ID NO:

1 (heavy chain variable region) and SEQ ID NO;

2 (light chain variable region) or has the following 6 CDRs;

SEQ ID NO;

3 (CDR-H1), SEQ ID NO;

4 (CDR-H2), SEQ ID NO;

5 (CDR-H3), SEQ ID NO;

6 (CDR-L1), SEQ ID NO;

7 (CDR-L2), or SEQ ID NO;

8 (CDR-L3), and a chemotherapeutic agent, to a subject having cancer in an effective amount to treat the cancer.

12. A method for treating a subject, comprising

systemically administering an isolated antibody or antibody fragment that selectively binds to ABCB5 and a chemotherapeutic agent to a subject having cancer in an effective amount to treat the cancer.