Proteins which induce immunological effector cell activation and chemattraction

• US 5,049,659 A
• Filed: 02/09/1988
• Issued: 09/17/1991
• Est. Priority Date: 02/09/1988
• Status: Expired due to Term

• Current Assignee: Dana-Farber Cancer Institute
• Original Assignee: Dana-Farber Cancer Institute
• Inventors: Patarca, Roberto M., Schwartz, Joel L., Cantor, Harvey I.
• Primary Examiner(s): Moskowitz, Margaret
• Assistant Examiner(s): Ossanna, Nina
• Application Number:
  US07/153,887
• Time in Patent Office: 1,316 Days
• Field of Search: 530/350, 530/351, 424/85.1
• US Class Current: 530/351
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons

Abstract

The present invention relates to genes and their encoded proteins which induce immunological effector cell activation and chemattraction. The proteins of the invention attract subsets of immunological effector cells and stimulate them to express their specialized effector cell functions. Such proteins, termed Ap-1 proteins, are expressed by lymphoid cells, and bind to effector cells such as macrophages and mast cells. In particular, the Ap-1 proteins induce macrophage phagocytosis, expression of class II major histocompatibility molecules, cytotoxicity, and migration, and induce hematopoietic progenitor cell differentiation. The Ap-1 molecules can be of value in the therapy or diagnosis of inflammatory or immune disorders, or neoplasia.

Claims

1. An essentially pure protein comprising a protein expressed by lymphoid cells, which protein is encoded by a DNA sequence as depicted in FIG. 2B, which is characterized by the ability to bind to mast cells, macrophages and T lymphocytes.

3. The protein of claim 1 or 2 which is murine.

4. The protein of claim 1 which is glycosylated.

7. The protein of claim 1 which is unglycosylated.

10. The protein of claim 1 or 2 which is produced recombinatly in a bacterium.

11. The protein of claim 1 or 2 which is produced recombinatly in a mammalian cell.

12. The protein of claim 1 or 2 which is produced recombinatly in a yeast.

13. The protein of claim 1 which is characterized by at least one of the following properties:

(i) macrophage activation;

(ii) macrophage chemattraction;

(iii) induction of macrophage cytotoxicity; and

(iv) induction of granulocyte/monocyte progenitor cell differentiation.

2. An essentially pure protein comprising a protein having the amino acid sequence as depicted in FIG. 2B, which is characterized by the ability to bind to mast cells, macrophages and T lymphocytes.

5. The protein of claim 2 which is glycosylated.

6. The protein of claim 5 which has a molecular weight of approximately 60 kilodaltons as determined by SDS-polyacrylamide gel electrophoresis.

8. The protein of claim 2 which is unglycosylated.

9. The protein of claim 8 which has a molecular weight of approximately 32 kilodaltons.

14. The protein of claim 2, which is characterized by at least one of the following properties:

(i) macrophage activation;

(ii) macrophage chemattraction;

(iii) induction of macrophage cytotoxicity; and

(iv) induction of granulocyte/monocyte progenitor cell differentiation.

15. An essentially pure protein encoded by the vector pCD-Ap-1 as contained in the recombinant bacterium deposited with the ATCC and assigned accession number 67615, which protein is characterized by the ability to bind to mast cells, macrophages and T lymphocytes.

25. The protein of claim 15 or 16 which is further characterized by at least one of the following properties:

(i) macrophage activation;

(ii) macrophage chemattraction;

(iii) induction of macrophage cytotoxicity; and

(iv) induction of granulocyte/monocyte progenitor cell differentiation.

16. An essentially pure protein encoded by the vector Hi92 as contained in the recombinant bacterium deposited with the ATCC and assigned accession number 67616, which protein is characterized by the ability to bind to mast cells, macrophages and T lymphocytes.

17. The protein of claim 16 which is human-derived.

18. The protein of claim 16 which is glycosylated.

19. The protein of claim 16 which is unglycosylated.

20. The protein of claim 16 which is produced recombinatly in a bacterium.

21. The protein of claim 17 which is produced recombinatly in a bacterium.

22. The protein of claim 16 which is produced recombinatly in a mammalian cell.

23. The protein of claim 17 which is produced recombinatly in a mammalian cell.

24. The protein of claim 16 which is produced recombinatly in a yeast.