Chimeric immunoreceptor useful in treating human gliomas

• US 7,514,537 B2
• Filed: 11/16/2005
• Issued: 04/07/2009
• Est. Priority Date: 04/30/2001
• Status: Expired due to Term

• Current Assignee: City of Hope
• Original Assignee: City of Hope
• Inventors: Jensen, Michael
• Primary Examiner(s): Kemmerer; Elizabeth C.
• Assistant Examiner(s): Howard; Zachary C
• Application Number:
  US11/274,344
• Publication Number:
  US 20060067920A1
• Time in Patent Office: 1,238 Days
• Field of Search: None
• US Class Current: 530/387.3
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/5437 IL-13
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/7155 for interleukins [IL]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The present invention relates to chimeric transmembrane immunoreceptors, named “zetakines,” comprised of an extracellular domain comprising a soluble receptor ligand linked to a support region capable of tethering the extracellular domain to a cell surface, a transmembrane region and an intracellular signaling domain. Zetakines, when expressed on the surface of T lymphocytes, direct T cell activity to those specific cells expressing a receptor for which the soluble receptor ligand is specific. Zetakine chimeric immunoreceptors represent a novel extension of antibody-based immunoreceptors for redirecting the antigen specificity of T cells, with application to treatment of a variety of cancers, particularly via the autocrin/paracrine cytokine systems utilized by human maligancy. In a preferred embodiment is a glioma-specific immunoreceptor comprising the extracellular targeting domain of the IL-13Rα2-specific IL-13 mutant IL-13(E13Y) linked to the Fc region of IgG, the transmembrane domain of human CD4, and the human CD3 zeta chain.

Claims

1. A chimeric immunoreceptor encoded by a nucleic acid sequence comprising SEQ ID NO:

15.

2. A method for treating human cancer, comprising adininistering to a human suffering from a glioma that overexpresses IL13α

2 receptor a plurality of T lymphocyte cells expressing the immunoreceptor of claim 1.

3. A vector which comprises a nucleic acid sequence comprising SEQ ID NO:

15.

4. A vector which consists essentially of SEQ ID NO:

14.