Mutant Forms of Fas Ligand and Uses Thereof

Abstract

The invention provides for DNA encoding Fas ligand muteins and chimeras and the proteins encoded thereby. The invention further includes the use of DNA and vectors to produce transformed cells expressing the mutant or chimeric Fas ligand. When the Fas ligand of the invention is a non cleavable form, the cells expressing the Fas ligand are useful in vitro for identifying Fas expressing cells or in vivo for reducing populations of Fas expressing cells. Thus, in other embodiments, the present invention is also directed to a method for treating a patient, for example a mammal, for autoimmune disease or transplant rejection by administering a Fas ligand therapeutic agent. The therapeutic agent is a polypeptide, a polynucleotide encoding the polypeptide or a small molecule. The polypeptides include full-length Fas ligand polypeptide, or a biologically active variant, derivative, portion, fusion or peptide thereof.

Description

[0001]This application is a divisional of application Ser. No. 10 / 404,466, filed Apr. 1, 2003, which is a divisional of application Ser. No. 08 / 968,686 filed Nov. 12, 1997, now U.S. Pat. No. 6,544,523, which claims the benefit of provisional application Ser. No. 60 / 039,972, filed Feb. 10, 1997 and provisional application Ser. No. 60 / 030,871 filed Jan. 13, 1996, which are hereby incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]The invention relates to Fas ligand muteins and chimeric proteins that act as Fas ligand agonists, and the DNA encoding the same. More particularly, the present invention relates to novel forms of Fas ligand, which when expressed in a transformed host cell, are surface bound in a conventional type II prohormone form but non-cleavable therefrom. These non-cleavable forms of Fas ligand and the transformed host cells expressing them are useful in diagnostic assays and in reducing populations of Fas expressing cells (e.g., activated T ...

AI Technical Summary

Benefits of technology

[0024]Another aspect of the invention is a method for reducing a population of activated T-cells or activated B-cells that comprises transforming a cell to express a non-cleavable Fas ligand polypeptide that remains membrane-bound thereto, wherein the transformed cell also bears a second ligand recognized by the activated T-cells or activated B-cells, and re-introducing this transformed cell into the population of activated T-cells or activated B-cells.

Problems solved by technology

Treatment of autoimmune diseases present a unique challenge to molecular biology and medical research.

Although various ameliorative and palliative therapies exist for some autoimmune diseases, and while the autoimmune diseases can spontaneously regress in a remission, effective treatment has yet to be developed for treating autoimmune diseases.