Cell targeting methods and compositions

• US 9,321,992 B2
• Filed: 06/13/2003
• Issued: 04/26/2016
• Est. Priority Date: 06/14/2002
• Status: Expired due to Fees

• Current Assignee: Case Western Reserve University
• Original Assignee: Case Western Reserve University
• Inventors: Dennis, James E., Caplan, Arnold I., Cohen, Nir
• Primary Examiner(s): HADDAD, MAHER M
• Application Number:
  US10/461,887
• Publication Number:
  US 20040048370A1
• Time in Patent Office: 4,701 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C12N 5/0006 Modification of the membrane of cells, e.g. cell decoration
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage

Abstract

In certain aspects, the invention relates to cell delivery compositions comprising a chondrogenic cell and a targeting moiety. Such compositions may be used, for example, in administering a targeted cell therapy to a subject.

Claims

1. A composition for targeting a chondrogenic cell to a cartilage matrix comprising:

a chondrogenic cell; and

a targeting moiety that binds to an epitope of cartilage matrix, said targeting moiety being selected from the group consisting of an antibody and an antibody fragment;

wherein said chondrogenic cell is linked to said targeting moiety, and

wherein the linked targeting moiety enhances adherence of the chondrogenic cell to cartilage matrix when administered to a cartilage matrix injury site and wherein the linked targeting moiety does not adversely affect chondrogenic cell viability, mitotic potential, and phenotype.

2. The composition of claim 1, wherein said antibody is a monoclonal antibody.

3. The composition of claim 1, wherein said antibody is a polyclonal antibody.

4. The composition of claim 1, wherein said antibody is selected from the group consisting of anti-collagen type II, anti-chondroitin 4-sulfate and anti-keratan sulfate.

5. The composition of claim 1, wherein said antibody is modified with a hydrophobic moiety.

6. The composition of claim 5, wherein said hydrophobic moiety is a palmitoyl moiety.

7. The composition of claim 5, wherein said hydrophobic moiety is a myristoyl moiety.

8. The composition of claim 1, wherein said antibody fragment is selected from the group consisting of Fv fragment, single chain Fv (scFv) fragment, Fab′

fragment, F(ab′

)2 fragment, single domain antibody, camelized antibody, humanized antibody, diabodies, tribodies, and tetrabodies.

9. The composition of claim 1, wherein said chondrogenic cell is linked to said targeting moiety directly.

10. The composition of claim 1, wherein said chondrogenic cell is linked to said targeting moiety via a linker.

11. The composition of claim 10, wherein said linker is selected from the group consisting of protein G and protein A.

12. A composition for targeting a chondrogenic cell to a cartilage matrix comprising:

a chondrogenic cell; and

an antibody that binds to an of epitope of cartilage matrix, the antibody being selected from the group consisting of anti-collagen type II antibodies, anti-chondroitin 4-sulfate antibodies, and anti-keratan sulfate antibodies;

wherein said chondrogenic cell is linked to said antibody by a palmitoyl moiety, and wherein the linked antibody enhances adherence of the chondrogenic cell to cartilage matrix when administered to a cartilage matrix injury site and does not adversely affect chondrogenic cell viability, mitotic potential, and chondrogenic phenotype.

13. The composition of claim 12, wherein said antibody is a monoclonal antibody.

14. The composition of claim 12, wherein said antibody is a polyclonal antibody.

15. The composition of claim 12, wherein said antibody is selected from the group consisting of Fv fragment, single chain Fv (scFv) fragment, Fab′

fragment, F(ab′

)2 fragment, single domain antibody, camelized antibody, humanized antibody, diabodies, tribodies, and tetrabodies.

16. A composition for targeting a chondrogenic cell to a cartilage matrix comprising:

a chondrogenic cell;

a first antibody that binds to an epitope of cartilage matrix, the first antibody comprising an anti-collagen type II antibody;

a second antibody that binds to an epitope of cartilage matrix, the second antibody comprising an anti-chondroitin 4-sulfate antibody;

wherein said chondrogenic cell is linked to the antibodies by a palmitoyl moiety, and wherein the linked antibodies enhance adherence of the chondrogenic cell to cartilage matrix when administered to a cartilage matrix injury site and do not adversely affect chondrogenic cell viability, mitotic potential, and chondrogenic phenotype.

17. A composition for targeting a chondrogenic cell to a cartilage matrix comprising:

a chondrogenic cell;

a first antibody that binds to an epitope of cartilage matrix, the first antibody comprising an anti-collagen type II antibody;

a second antibody that binds to an epitope of cartilage matrix, the second antibody comprising an anti-chondroitin 4-sulfate antibody; and

a third antibody that binds to an epitope of cartilage matrix, the third antibody comprising an anti-keratan sulfate antibody;

wherein said chondrogenic cell is linked to the antibodies by a palmitoyl moiety, and wherein the linked antibodies enhance adherence of the chondrogenic cell to cartilage matrix when administered to a cartilage matrix injury site and do not adversely affect chondrogenic cell viability, mitotic potential, and chondrogenic phenotype.