Chimeric nucleic acids encoding polypeptides comprising TNF alpha, CD70 and FAS ligand domains

US7964712B2 · kind B2 · utility

Assignee

• The Regents of the University of California · US

Inventors

• Charles E. Prussak · San Diego, US
• Thomas J. Kipps · San Diego, US
• Mark J. Cantwell · San Diego, US

Key dates

• Filing date: Aug 30, 2010
• Grant date: Jun 21, 2011
• Expiry date: Aug 30, 2030

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNFα, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNFα, wherein the encoded domain or subdomain replaces a cleavage site of native TNFα, and a second nucleotide sequence encoding a domain or subdomain of native TNFα that binds to a TNFα receptor. The encoded chimeric TNFα 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 TNFα receptor on the surface of a cell. The chimeric TNFα is therefore useful in methods for inducing apoptosis of a cell expressing a TNFα 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 TNFα that is expressed on the surface of the cell.