DNA construct encoding CE7-specific chimeric T cell receptor

• US 7,446,191 B2
• Filed: 02/08/2008
• Issued: 11/04/2008
• Est. Priority Date: 04/11/2001
• Status: Expired due to Term

• Current Assignee: City of Hope
• Original Assignee: City of Hope
• Inventors: Jensen, Michael
• Primary Examiner(s): Blanchard; David J.
• Application Number:
  US12/028,442
• Publication Number:
  US 20080160607A1
• Time in Patent Office: 270 Days
• Field of Search: None
• US Class Current: 536/23.4
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C07K 2319/03 containing a transmembrane segment
• 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

Genetically engineered, CE7-specific redirected immune cells expressing a cell surface protein having an extracellular domain comprising a receptor which is specific for CE7, an intracellular signaling domain, and a transmembrane domain, and methods of use for such cells for cellular immunotherapy of CE7⁺ neuroblastoma are disclosed. In one embodiment, the immune cell is a T cell and the cell surface protein is a single chain FvFc: receptor where Fv designates the V_H and V_L chains of a single chain monoclonal antibody to CE7 linked by peptide, Fc represents a hinge-C_H2-C_H3 region of a human IgG₁, and represents the intracellular signaling domain of the zeta chain of human CD3. DNA constructs encoding a chimeric T-cell receptor and a method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor are also disclosed.

Claims

1. A DNA construct encoding a CE7-specific chimeric T cell receptor wherein the CE7-specific chimeric T cell receptor comprises an intracellular signaling domain, a transmembrane domain and an extracellular domain, the extracellular domain comprising a CE7-specific receptor and wherein the CE7-specific chimeric T cell receptor comprises amino acids 21-631 of SEQ ID NO:

2.

2. An expression vector containing a DNA construct of claim 1 in proper orientation for expression.