Patent Number: 7,786,282

Title: Nucleic acid molecules encoding TNF-.alpha. ligand polypeptides having a CD154 domain

Abstract: The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF.alpha. and chimeric TNF.alpha. polypeptides. The former have a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF.alpha., wherein the encoded domain or subdomain lacks a cleavage site, and a second nucleotide sequence encoding a domain or subdomain of native TNF.alpha. that binds to a TNF.alpha. receptor. The encoded chimeric TNF.alpha. is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF.alpha. receptor on the surface of a cell. The chimeric TNF.alpha. is therefore useful in methods for inducing apoptosis of a cell expressing a TNF.alpha. receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF.alpha. that is expressed on the surface of the cell.

Inventors: Prussak; Charles E. (San Diego, CA), Kipps; Thomas J. (Rancho Santa Fe, CA), Cantwell; Mark J. (San Diego, CA)

Assignee: The Regents of the University of California

International Classification: C12N 15/12 (20060101); C12N 15/11 (20060101); C12N 15/63 (20060101); C12N 5/10 (20060101)

Expiration Date: 8/31/12018