Increased T-cell tumor infiltration by mutant light

• US 20050025754A1
• Filed: 06/10/2004
• Published: 02/03/2005
• Est. Priority Date: 06/11/2003
• Status: Active Grant

• Current Assignee: University of Chicago
• Original Assignee: University of Chicago
• Inventors: Fu, Yang-Xin
• Granted Patent: US 7,807,784 B2
• Time in Patent Office: Days
• US Class Current: 424/93.210
• CPC Class Codes: A61K 2039/5152 Tumor cells
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 2319/43 containing a FLAG-tag
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus

Abstract

Mutant LIGHT expressed in a tumor environment elicited high levels of chemokines and adhesion molecules, accompanied by massive infiltration of naïve T lymphocytes. Methods and compositions to elicit immune responses against tumors including tumor volume reduction and reduced metastasis using mutant LIGHT are disclosed.

Claims

1. A method to induce effective anti-tumor activity of T-cells against a tumor, the method comprising:

(a) introducing a cDNA molecule encoding mutant LIGHT into the tumor; and

(b) expressing the cDNA molecule.

2. A therapeutic vaccine comprising mutant LIGHT-expressing tumor cells.

3. A prophylactic vaccine comprising mutant LIGHT and tumor antigens in tumor cells.

4. A method to destroy or reject a tumor by creating lymphoid-like microenvironments that express chemokines, adhesion molecules, and costimulatory molecules required for priming naï

ve T-cells, the method comprising;

(a) introducing a cDNA molecule encoding mutant LIGHT into the tumor; and

(b) expressing the cDNA molecule.

5. The method of claim 4, wherein the tumor is a solid tumor.

6. A mutant cDNA that does not encode a proteolytic site EKLI from positions 79 to 82 of the LIGHT protein.

7. A mutant LIGHT protein having the amino acid sequence from positions 85-239 of LIGHT and a flag sequence.

8. The mutant LIGHT protein of claim 7 is a recombinant protein.

9. A mutant LIGHT protein that does not have a site for protease digestion.

10. A host cell transformed with mutant LIGHT.

11. A vector with the mutant LIGHT cDNA molecule.

12. The vector of claim 11 is an adenoviral vector.

13. A method to screen candidate anti-tumor compounds, the method comprising:

(a) obtaining mutant LIGHT expressing cells and control cells;

(b) administering the candidate anti-tumor compounds to the LIGHT expressing and control cells; and

(c) determining whether there is loss or death of tumor cells in the mutant LIGHT expressing cells as compared with control cells.