# US 6,159,701 A · Method and compositions for treating and diagnosing tumors using adenosine receptor activated cells

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- Number: US 6,159,701 A
- Document ID: US6159701A
- Status: Granted
- Kind: A
- Application number: 08/748,559
- Filed: 1996-11-08
- Granted: 2000-12-12
- Earliest claimed: 1996-11-08
- Assignees: Link Technology Incorporated
- Inventors: Constance Neely
- Web page: https://patentgrep.com/patent/US6159701A

## CPC

- A61K 51/0491: {Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers}
- A61P 35/00: Antineoplastic agents
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods of treating and/or imaging tumors utilize A.sub.1 adenosine-receptor activated cells (such as monocytes and macrophages) are described. Activated cells may be administered systemically or locally, and may be radiolabelled to provide imaging and diagnostic functions. Macrophages resident in tissues may be primed and activated for use in treating and imaging tumors.

## Claims

### Claim 1

A method of imaging tumor cells in vivo in a subject, comprising:
(a) obtaining a sample of treatment cells from a subject, said treatment cells selected from the group consisting of macrophages, monocytes and splenocytes;
(b) priming said treatment cells by contact with a priming agent in an amount sufficient to prime said treatment cells;
(c) labeling said treatment cells with a radiolabelled A1 adenosinc receptor agonist, said A1 adenosine receptor agonist provided in an amount sufficient and for a time sufficient to induce cytotoxicity in said treatment cells; and then
(d) administering said labelled treatment cells to the subject in an amount effective to provide a radioimage of tumor cells present in said subject.

### Claim 2 (depends on 1)

The method of claim 1 wherein said selective A.sub.1 adenosine receptor ligand is a selective A.sub.1 adenosine receptor agonist in an amount sufficient to induce cytotoxicity in said treatment cells.

### Claim 3 (depends on 1)

The method of claim 1 wherein said treatment cells are monocytes, and said monocytes are cultured to provide macrophages for priming in step (b).

### Claim 4 (depends on 1)

The method of claim 1 wherein said priming agent is selected from the group consisting of phorbol myristoyl acetate (PMA), lipopolysaccharide (LPS), interferon gamma (IFN.tau.), granulocyte-macrophage colony stimulating factor (GMCSF), and f-met-leu-phe (FMLP).

### Claim 5 (depends on 1)

The method of claim 1 wherein said subject is human.

### Claim 6 (depends on 1)

The method of claim 1 further comprising contacting said treatment cells to an allosteric enhancer in an amount effective to enhance the binding of A.sub.1 adenosine receptor agonists to A.sub.1 adenosine receptors.

### Claim 7 (depends on 1)

The method of claim 1 further comprising contacting said treatment cells to dexamethasone in an amount effective to increase the number of A.sub.1 adenosine receptor receptors on said treatment cells.

### Claim 8 (depends on 1)

The method of claim 1 further comprising contacting said treatment cells to a protein kinase inhibitor.

### Claim 9 (depends on 1)

The method of claim 1 further comprising the step of contacting said treatment cells to an A.sub.2 adenosine receptor antagonist.

### Claim 10 (depends on 1)

The method of claim 1 further comprising, prior to step (b), subjecting said treatment cells to a period of hypoxia and re-oxygenation sufficient to increase A.sub.1 adenosine receptor activity.

### Claim 11 (depends on 1)

The method of claim 1 wherein said administering step is carried out by administering said labelled treatment cells systemically to the subject.

### Claim 12 (depends on 1)

The method of claim 1 wherein said administering step is carried out by administering said labelled treatment cells directly to tissue suspected of containing tumor cells.