NEW FAS LIGAND WITH IMPROVED THERAPEUTIC POTENTIAL

The fas ligand (fasL) induces programmed cell death in fas-bearing cells. The fasL/fas interaction appears critical to the regulation of cell number in a large and ever-expanding number of organ systems, including the immune system, where it has received considerable scientific attention. FasL expression has been shown to limit the immune response in certain situations by eliminating antigen-specific fas-bearing activated T cells and possibly other fas-bearing inflammatory cell types. This observation raises the possibility of using fasL expression to ameliorate autoimmune disease or to confer immune privilege to transplanted organs or otherwise immunogenic gene therapy vectors. Moreover, some cancer cells synthesize fas and delivery of fasL to these cells has been shown to induce tumor cell death. However, one of the main obstacles to the therapeutic use of the fas ligand is the very real possibility of unwanted, nonspecific local and even systemic tissue damage. Indeed, measurable levels of soluble fasL have been demonstrated in the serum of patients with a subset of lymphomas, and have been implicated in the hepatitis and granulocytopenia in these patients.

To this end, scientists at UCSF have developed a form of fasL which incorporates two features that should enhance its therapeutic potential for multiple indications. In particular, not only does the modified fasL exhibit none of the toxicity to hepatocytes characteristic of naturally-occurring fasL, but also cells bearing the modified fasL are twice as active in killing fas-bearing targets in vitro.

If you would like to receive further information about this technology and potential licensing opportunities, please contact:

Joel B. Kirschbaum, Ph.D.
Director & Senior Technology Portfolio Manager
(415) 353-4462 phone
(415) 348-1579 fax
Joel Kirschbaum, Ph.D.

Reference: OTM Case #SF97-089